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Review

Surface-Active Compounds Produced by Microorganisms: Promising Molecules for the Development of Antimicrobial, Anti-Inflammatory, and Healing Agents

by
Jéssica Araujo
1,2,†,
Joveliane Monteiro
1,2,†,
Douglas Silva
2,
Amanda Alencar
2,
Kariny Silva
2,
Lara Coelho
2,
Wallace Pacheco
2,
Darlan Silva
3,
Maria Silva
3,
Luís Silva
1,4 and
Andrea Monteiro
1,2,*
1
Rede de Biodiversidade e Biotecnologia da Amazônia Legal, BIONORTE, São Luís 65055-310, MA, Brazil
2
Laboratório de Microbiologia Aplicada, Universidade CEUMA, São Luís 65075-120, MA, Brazil
3
Laboratório de Ciências do Ambiente, Universidade CEUMA, São Luís 65075-120, MA, Brazil
4
Laboratório de Patogenicidade Microbiana, Universidade CEUMA, São Luís 65075-120, MA, Brazil
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Antibiotics 2022, 11(8), 1106; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11081106
Submission received: 3 July 2022 / Revised: 29 July 2022 / Accepted: 2 August 2022 / Published: 16 August 2022
(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products)
Review Reports Versions Notes

Abstract

:
Surface-active compounds (SACs), biomolecules produced by bacteria, yeasts, and filamentous fungi, have interesting properties, such as the ability to interact with surfaces as well as hydrophobic or hydrophilic interfaces. Because of their advantages over other compounds, such as biodegradability, low toxicity, antimicrobial, and healing properties, SACs are attractive targets for research in various applications in medicine. As a result, a growing number of properties related to SAC production have been the subject of scientific research during the past decade, searching for potential future applications in biomedical, pharmaceutical, and therapeutic fields. This review aims to provide a comprehensive understanding of the potential of biosurfactants and emulsifiers as antimicrobials, modulators of virulence factors, anticancer agents, and wound healing agents in the field of biotechnology and biomedicine, to meet the increasing demand for safer medical and pharmacological therapies.

1. Introduction

Microorganisms can produce several surface-active compounds (SACs) with hydrophilic and hydrophobic moieties. These structural features allow them to interact with the surface and interfacial tensions, form micelles, and emulsify immiscible substances [1,2].
Biosurfactants (BSs) and bioemulsifiers (BEs) are considered SACs because of their ability to interfere and with modifying surfaces. Because these biomolecules are amphiphilic and are produced by different microorganisms, they have different physicochemical properties and physiological roles, which contribute to their specific functions in nature and biotechnological applications [3].
Recently, the production of SACs has received extensive attention because of their diverse applications, such as dissolving water-insoluble compounds, heavy metal binding, contaminant desorption, inhibiting bacterial pathogenesis, adhesion, and cell aggregation [4,5,6,7,8]. In addition, SACs also have several advantages over synthetic surfactants, such as low toxicity, lower critical micelle concentration (CMC), higher biodegradability, and ecological acceptability [9].
Moreover, these compounds exhibit antibacterial [5,10], antifungal [11], antiviral [12], and antitumor activities [13]. Their antiadhesive properties and antibiofilm activities are also important in inhibiting the adhesion and colonization of pathogenic microorganisms and removing preformed biofilms on silicone discs and other biomedical instruments [14].
The present use of these biomolecules has aroused interest from several sectors because of their numerous functions and sustainable properties, allowing various applications in petroleum, food, medicine, pharmaceuticals, chemicals, pulp and paper, textiles, and cosmetics. Furthermore, because of their application in soil bioremediation, they are considered the “green molecules” of the 21st century [15].

2. Surface-Active Compounds

2.1. Biosurfactants

Biosurfactants (BSs), which are low molecular weight microbial compounds, are synthesized extracellularly or linked to the cell membrane of bacteria [16], yeasts [17], and filamentous fungi [18]. Produced under various extreme environmental conditions, their chemical compositions depend on the microorganism that produces them, raw materials, and process conditions [6].
Surfactants are amphiphilic molecules with a hydrophobic moiety comprising a hydrocarbon chain with saturated or unsaturated and hydroxylated fatty alcohols or fatty acids, and a hydrophilic moiety comprising hydroxyl, phosphate, or carboxyl groups, or carbohydrates (such as mono-, oligo-, or polysaccharides) or peptide fractions [3,19]. Depending on their biochemical nature, these compounds are classified as glycolipids, lipopeptides, lipoproteins or fatty acids, and phospholipid polymers, with glycolipids and lipopeptides being the most abundant [20,21].
Glycolipids consist of mono- or oligosaccharides and lipids, where different sugars (glucose, mannose, galactose, glucuronic acid, or rhamnose) link to form saturated or unsaturated fatty acids, hydroxylated fatty acids, or fatty alcohols. The most studied groups include sophorolipids (SLs), mannosylerythritol lipids, trehalolipids, and rhamnolipids (RLs) [22,23], which are usually produced by the yeast Starmerella bombicola [24], Pseudozyma sp. [25,26] Rhodococcus erythropolis [27] and Pseudomonas aeruginosa [28], respectively.
On the other hand, lipopeptides (LP) consist of cyclopeptides with amino acids linked to fatty acids of different chain lengths [29]. The most common among these are surfactin, iturin, and fengycin [29,30,31] which are produced by different microorganisms, such as the genera Bacillus [32], in turn, other lipopeptides have been detected in Bacillus amyloliquefaciens [33], Streptomyces sp. [34], Pseudomonas guguanensis [35], and Serratia marcescens [36].
Microorganisms that produce BS inhabit water (fresh, underground, and sea) and land (soil, sediments, and mangroves) and can grow in extreme environments (oil reservoirs) and under different temperatures, pH values, and salinity levels [37,38,39].
These microorganisms are generally heterotrophs that need carbon, nitrogen, minerals, vitamins, growth factors, and water to grow and produce metabolites. In general, carbon sources (carbohydrates, oils, and fats) and hydrocarbon groups are often consumed during BS production. For example, glucose, a carbon source easily metabolized by microorganisms through glycolysis to generate energy, is commonly reported as a factor in producing higher yields [37,40].
Because of their amphipathic nature, BSs can mix immiscible fluids, reduce surface and interfacial tensions, and promote solubility of polar compounds in nonpolar solvents [41] that help exhibit numerous properties, such as foaming, dispersion, wetting, emulsification, demulsification, and coating, making them suitable for physicochemical and biological remediation technologies of organic and metallic contaminants [42].
Biosurfactants due to their physicochemical properties have industrial applications in pharmaceuticals, textile processing, agriculture, cosmetics, personal care, and the food industry, as well as environmental applications in soil remediation, hydrocarbon degradation, and oil recovery [43,44,45].
Several BSs have antibacterial, antifungal, antiviral, or antitumor properties, making them potential alternatives to conventional therapeutics in many biomedical applications [45,46].
Despite their versatility and efficiency in terms of applicability in different fields, their production has always been a challenge because of inefficient bioprocessing and high costs due to the expensive substrates used [33]. Therefore, optimizing strategies on cost efficiency and high-yield bioprocessing is critical for low-cost production and mass commercialization.

2.2. Bioemulsifier (BE)

Unlike BSs, bioemulsifiers (BEs) have high molecular weight and can emulsify, even at low concentrations, two immiscible liquids, while not reducing surface or interfacial tension [47]. These comprise complex mixtures of heteropolysaccharides, lipopolysaccharides, proteins, glycoproteins, or lipoproteins, which guarantee better emulsification potential and emulsion stabilization [3,48,49].
Bioemulsifiers, which are synthesized by bacteria, yeasts, and filamentous fungi, can be isolated from contaminated soil, mangroves, seawater, freshwater, and human skin [50,51,52,53]. The most studied polymeric BEs include emulsan, alasan, liposan, mannoprotein, and other polysaccharide-protein complexes. Members of the genus Acinetobacter sp. are commonly reported to produce BEs [15].
Despite numerous reports on the production of BEs and BSs by different bacteria, the genus Acinetobacter spp. received special attention because it is the first known producer of BEs, with emulsan, biodispersan, and alasan as the best examples of BEs commercially produced by the genus. These BEs are mainly used in microbial oil recovery and the biodegradation of toxic compounds [15].
Compared with synthetic surfactants, BEs have many advantages as they are eco-friendly, biocompatible, less toxic with higher biodegradability, and active at extreme temperatures, pH values, and salinity levels. Furthermore, BEs can be produced from low-cost renewable substrates, such as industrial waste, vegetable oils, and hydrocarbons [53].
Various carbon sources are used in BE production, such as ethanol, n-hexadecane, crude oil, glucose, lactic acid, methylnaphthalene, peptone, n-heptadecane, edible oil, olive oil, glycerol, and C-heavy oil [54]. Conventionally, microbial production of BE is still expensive, with the use of synthetic sources as one of the factors contributing most to the high costs. One promising strategy to make the cost economically viable is to include renewable sources from agro-industrial residues and by-products. In this sense, previous research had explored several alternative low-cost substrates, such as residual soybean oil from frying and corn steep liquor, as alternatives to synthetic sources of carbon and nitrogen [53].
Despite their potential advantages, several obstacles hinder practical BE applications, including low yields and high purification costs. To address these issues, researchers have been striving to develop more cost-efficient BEs, which can be used at low concentrations [55].
Bioemulsifiers can form very stable emulsions and dispersions that do not mix, remain attached to the droplet interfaces, and can re-emulsify by adding or replacing a new solvent without diluting. Because of these advantages, BEs are preferred over BSs in the cosmetics and food industries [48].
Because of diverse functions, such as emulsification, wetting, foaming, cleaning, phase separation, surface activity, and hydrocarbon viscosity reduction, BEs are best suited for bioremediation, enhanced oil recovery, cleaning of pipe and vessels contaminated with oil, and more. In addition, emulsifiers are widely used in the food and drug industry [56].

2.3. Microorganisms Producing SACS

For many years, researchers have tirelessly searched for microorganisms that have the potential to produce secondary metabolites with surfactant or emulsifying properties. The amount of BS or BE produced depends on the type of microorganisms and their sources (Table 1).

3. Biological Properties

3.1. Antimicrobial Activities

The discovery of antibiotics in the last century can be considered a major advancement in medicine because the use of these antimicrobial agents significantly reduced morbidity and mortality associated with microbial infections. Antibacterial and antifungal factors reduce and eliminate the viability and growth of microbial populations through several mechanisms: (i) disruption of extracellular membranes and/or their cell wall, (ii) inhibition of gene expression, (iii) DNA damage, or (iv) manipulation of important metabolic pathways [74].
Bacteria become resistant to antimicrobial agents in several ways: through horizontal gene transfer between genetic elements of different strains and the environment that confer resistance and through mutations that interfere with basic cell functions in addition to conferring resistance to microorganisms [75,76].
The most resistant bacteria associated with serious hospital infections include Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, P. aeruginosa, and Enterobacter sp., which often result in high mortality rates [77]. Furthermore, other microorganisms such as Candida spp. can also be considered a global health threat because of their resistance to antimicrobial agents [78,79,80].
The increasing rates of antimicrobial resistance and the emergence of new microbial pathogens reinforce the need to find new antimicrobial compounds to fight microbial infections. Among these new strategies, SACs have promising antibiotic and disinfectant potential, as well as antibiotic delivery properties due to their physicochemical properties. Most of these biomolecules can break the outer and inner membranes of pathogens, thereby exploiting their charge and hydrophobicity. The advantages of using SACs as antimicrobials include their broad-spectrum bactericidal action and the absence of pathogen resistance mechanisms [81].
Cationic surfactants comprise the largest class of synthetic surfactants with antimicrobial properties because of their broad spectrum of biostatic and biocidal activities against planktonic pathogens. The hydrophobic chain of cationic surfactants penetrates the microbial cell membrane and interferes with membrane continuity and metabolic processes, leading to cell death [82]. Despite exhibiting antimicrobial efficiency mainly against Gram-positive bacteria (29–32 mm), such as S. aureus and Bacillus subtilis, these compounds are less biodegradable than natural surfactants [83].
Previous studies reported the antimicrobial efficacy of glycolipid SACs produced by microorganisms. For example, RLs produced by P. aeruginosa significantly inhibited the growth of S. mutans UA159 and S. sanguinis ATCC10556. Furthermore, they completely inhibited the growth of Aggregatibacter actinomycetemcomitans Y4 at high concentrations [7].
Similarly, the synergistic action of two RL BSs produced by P. aeruginosa C2 and Bacillus stratosphericus A15 demonstrated bactericidal activity by rupturing the membrane of gram-positive and gram-negative bacteria, such as S. aureus ATCC 25923 and Escherichia coli K8813 [84]. Because of these actions, the membrane disintegrates, leading to penetration into the cell wall and plasma membrane through the formation of pores, followed by leakage of internal cytoplasmic materials, leading to cell death [85].
A previous study demonstrated that the synergism between essential oils of oregano, cinnamon tree, and lavender with RLs produced by P. aeruginosa increased the antimicrobial effect against Candida albicans and S. aureus which are resistant to methicillin [86], revealing that SAC activity can be enhanced when they establish a synergistic relationship with other compounds. In addition to RLs, SLs are also easily extracted and are usually produced by Candida spp. yeast [87] either in the lactone form or the acid form or as a mixture of both forms [88,89].
A previous study showed that SL produced by C. albicans SC5314 and Candida glabrata CBS138 showed antibacterial properties against pathogenic bacteria Bacillus subtilis and E. coli [10]. Besides its antibacterial activity against both Gram-positive and Gram-negative bacteria, this class of BS also exhibited promising antifungal activity against pathogenic fungi including Colletotrichum gloeosporioides, Fusarium verticillioides, Fusarium oxysporum, Corynespora cassiicola, and Trichophyton rubrum [90].
The antimicrobial activity of SACs glycolipids was found to be dependent on the type of glycolipid and the interaction with the cell membrane. Diaz de Renzo et al. [63] demonstrated that RLs inhibit bacterial growth in the exponential phase while SLs inhibit growth between the exponential and stationary phases.
The antimicrobial potential of lipopeptide SACs has also been recognized; these biomolecules correspond to the most important components of metabolites that are synthesized by many species of the genus Bacillus spp., which characterize the strains of this genus as important parts of plant disease control and food safety [91,92,93].
Antimicrobial lipopeptides, such as iturin, fengycin, and surfactin, have been identified in Bacillus velezensis HC6. Surfactin exhibited strong antibacterial effects against Listeria monocytogenes and Bacillus cereus, while fengycin and iturin inhibited the growth of pathogenic fungi Aspergillus flavus, Aspergillus parasiticus, Aspergillus sulphureus, Fusarium graminearum, and Fusarium oxysporum [94]. Researchers also found that when B. velezensis HC6 is applied to corn, it reduced the levels of aflatoxin and ochratoxin produced by fungi.
Ohadi et al. [95] demonstrated that lipopeptides produced by Acinetobacter junii displayed nonselective activity against Gram-positive and Gram-negative bacterial strains. The data showed that this bioproduct had effective antibacterial activity at concentrations almost below the CMC and that the minimal inhibitory concentration (MIC) values were lower than the standard antifungal activity, exhibiting almost 100% inhibition against Candida utilis.
Other broad classes of bacterial metabolites with surface-active potential and antimicrobial effects include glycoproteins, peptides, and fatty acids. Lactobacillus spp. produced a bioactive glycolipoprotein surfactant with antimicrobial activity against C. albicans using sugarcane molasses as substrate, and some pathogenic gram-positive and gram-negative bacteria [96]. A cyclic heptapeptide containing a fatty acid moiety produced by Bacillus subtilis, called bacaucin 1, exhibited specific antibacterial activity against methicillin-resistant S. aureus (MRSA) by disrupting the membrane without detectable toxicity to mammalian cells or induction of bacterial resistance. In addition, this peptide was found to be efficient in preventing infections in both in vitro and in vivo models [97].
Finally, some microorganisms excrete mixtures of bioactive compounds with surface-reducing ability and emulsifying potential. For example, the actinomycete strains of Streptomyces griseoplanus NRRL-ISP5009 produced a BS component that is a complex mixture of proteins, carbohydrates, and lipids that have antimicrobial activity against gram-positive bacteria (Bacillus subtilis, S. aureus) and pathogenic fungi (C. albicans and Aspergillus fumigatus). However, it is only moderately active against Gram-negative bacteria E. coli and Salmonella typhimurium [37].

3.2. Antiviral Activity

Viruses represent a serious threat to human health at a global level. Previous studies have described secondary metabolites with surface-active properties for their antiviral properties against a variety of viruses. Antiviral activity by SACs was shown to be effective against various viruses, enveloped and nonenveloped (Table 2).
Viral infections represent one of the main causes of human and animal morbidity and mortality that lead to significant healthcare costs [107]. Therefore, secondary metabolites with surface-active properties should be considered promising substances for the development of antiviral compounds.

3.3. Anti-Inflammatory Activity

Inflammatory responses represent a crucial aspect of a tissue’s response to certain injuries, chemical irritation, or microbial infections. This complex response involves leukocyte cells, macrophages, neutrophils, and lymphocytes. In response to inflammation, these cells release specialized substances, including amines and vasoactive peptides, eicosanoids, pro-inflammatory cytokines, and acute-phase proteins, which mediate the inflammatory process and prevent additional tissue damage [108].
Currently, studies on SACs are looking into their potential as anti-inflammatory drugs. For example, a recent in vivo study showed that surfactin inhibited the pro-inflammatory response in Zebrafish larvae (Danio rerio), significantly reducing the expression of interleukin (IL)-1β, IL-8, tumor necrosis factor-α (TNF-α), nitric oxide (NO), nuclear factor kappa-β p65 (NF-κBp65), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and increasing the expression of IL-10. Furthermore, the study showed that surfactin reduced neutrophil migration and alleviated liver damage [109].
Other studies showed that surfactin systematically induced CD4 + CD25 + FoxP3 + Tregs in the spleen of mice, which inhibit T cells from producing pro-inflammatory cytokines such as TNF-α and interferon (IFN)-γ. Moreover, surfactin attenuation of chronic inflammation increased IL-10 expression in atherosclerotic lesions of the aorta of mice, demonstrating that BSs can restore the balance in the Th1/Th2 response in mice [110], as well as induce the maturation of dendritic cells (DCs) and increase the expression of MHC-II molecules and other costimulatory factors [111].
Few anti-inflammatory properties related to glycolipid BSs have been reported. Sophorolipids produced by C. bombicola reduced lipopolysaccharide-induced expression of TNF-α, COX-2, and IL-6 in RAW 264.7 cells [112], and reduced the level of immunoglobulin E (IgE), TLR-2, IL-6, and STAT3 mRNA expression [113].
In previous in vivo models, SLs reduced sepsis-related mortality and exhibited anti-inflammatory effects in mice by inhibiting nitric oxide and inflammatory cytokine production [114,115]. On the other hand, the glycolipid complex had no significant effect on the proliferative effect of peripheral blood leukocytes because it activated the production of pro-inflammatory cytokines (IL-1β and TNF-α) without affecting the IL-6 production in vitro in the monocyte fraction [116].

3.4. Anticancer Activity

Cancer is considered a multistage disease, the etiology of which is associated with high incidence and mortality rates globally. Chemotherapy drugs, surgery, and radiation remain the most common treatments to fight the disease in humans. However, they are all associated with serious adverse effects, indicating the lack of specificity and the need to discover new antitumor agents to improve the effectiveness of conventional chemotherapy drugs while reducing the adverse effects [74].
For these purposes, several studies have demonstrated the antitumor potential of several SACs (Table 3). Biosurfactants have been proposed as suitable drug candidates for many diseases including cancer [117]. Given their wide applications, the interest in exploring their role in promoting human health continues to grow.

3.5. Antibiofilm Activity

Biofilms comprise microbial communities attached to the surface and embedded in an extracellular matrix composed of extracellular polymeric substances (EPS) secreted by cells that reside within them. In general, EPS is a mixture of polysaccharides, proteins, extracellular DNA (eDNA), and other smaller components. The biofilm matrix constituents’ physical and chemical properties enable the matrix to protect resident cells from desiccation, chemical disturbance, invasion by other bacteria, and death from predators. However, biofilms often cause major medical problems and are the cause of chronic infections because biofilm communities can house bacteria that are tolerant and persistent against antibiotic treatment and are more resistant to antibiotics compared with planktonic bacteria [9,122].
Because of their composition, biofilms cause a wide range of chronic diseases due to the emergence of antibiotic-resistant bacteria that have become difficult to treat effectively. To date, available antibiotics are ineffective in treating these biofilm-related infections because of their higher MIC and minimal bactericidal concentration values, which may lead to in vivo toxicity. Therefore, designing or tracking antibiofilm molecules that can effectively minimize and eradicate biofilm-related infections is important [123].
Because of their antimicrobial, antiadhesive, and antibiofilm properties, SACs can be used to neutralize biofilm formation and the emergence of drug-resistant microorganisms [14]. These biomolecules tend to interact with antimicrobials [124,125], which are usually less effective against biofilms in general and multispecies biofilms associated with extremely complicated polymicrobial infections.
A mixture of lipopeptides (surfactin, iturin, and fengycin), which are synthesized by B. subtilis, prevented biofilm formation by inhibiting cell adhesion of Trichosporon spp. by up to 96.89% and dispersed mature biofilms (up to 99.2%), reducing their thickness and cell viability. This mixture reduced cell ergosterol content and altered the membrane permeability and surface hydrophobicity of planktonic cells [126].
Another mixture of lipopeptides (surfactin, iturin, and lichenysin) was identified for the first time in Lactobacillus spp. vaginal exhibited strong antiadhesive activity (up to 74.4%) against the biofilm producer C. albicans [67]. Mixed lipopeptides (iturin, fengycin, and surfactin) with higher surfactin content produced by B. subtilis TIM10 and B. vallismortis TIM68 inhibited the biofilm formation of Malassezia spp., especially TIM10, by about 90% [127].
Meanwhile, surfactin-type BS produced by B. subtilis reduced adhesion and stopped the formation of S. aureus biofilm on glass, polystyrene, and stainless-steel surfaces. Surfactin significantly decreased biofilm percentage and reduced icaA and icaD expressions, which are important for staphylococcal biofilm structure. Furthermore, lipopeptides have been shown to affect the quorum sensing (QS) system in S. aureus by regulating the autoinducer 2 activity [94].
In terms of the antibiofilm activity of glycolipids, Allegrone et al. [128] reported the effects of different types of RLs. They demonstrated that RL produced by P. aeruginosa 89 (R89BS) was 91.4% pure and comprised 70.6% of monorhamnolipids and 20.8% of dirhamnolipids. The pure extract R89BS inhibited S. aureus adhesion (97%) and biofilm formation (85%). Furthermore, purified monorhamnolipids (mR89BS) have been observed to induce dispersion of preformed biofilms at all concentrations (0.06–2 mg/mL) by 80%–99%, unlike the pure extract R89BS and purified dirhamnolipids (dR89BS), which depended on the tested concentration.
Ceresa et al. [5] demonstrated that R89BS-coated silicone elastomeric disks significantly neutralized Staphylococcus spp. biofilm formation in terms of accumulated biomass (up to 60% inhibition in 72 h) and cellular metabolic activity (up to 68% inhibition in 72 h). The results suggested that RL coatings may be an effective antibiofilm treatment procedure and represent a promising strategy for preventing infections associated with implantable medical devices.
Shen et al. [129] demonstrated that besides inhibiting the formation of new biofilms, RLs were superior in eradicating mature biofilms formed by Helicobacter pylori, E. coli, and Streptococcus mutans in a dose-dependent manner, compared with other antibacterial agents even at concentrations below minimum inhibitory concentrations (MICs). They can enhance the effect of antimicrobial agents. Sidrim et al. [130] observed that these molecules significantly increased the activity of meropenem and amoxicillin-clavulanate against mature Burkholderia pseudomallei biofilms.
Rhamnolipids produced by P. aeruginosa SS14 also inhibited planktonic cells of filamentous fungi of Trichophyton rubrum and Trichophyton mentagrophytes. The formation and rupture of mature biofilms were dose-dependent, with the highest activity observed at concentrations of 2 × MIC against both pathogens [131].
Like RLs, SLs exhibited an effective inhibitory activity against biofilm formation. Ceresa et al. [132] obtained three different SL products: SLA (acid congeners), SL18 (lactonic congeners), and SLV (mixture of acid and lactone congeners), which all showed an inhibitory effect of 70%, 75%, and 80% for S. aureus, P. aeruginosa, and C. albicans, respectively. Using 0.8% w/v SLA on pre-coated medical silicone disks reduced S. aureus biofilm formation by 75%. In co-incubation experiments, 0.05% w/v SLA significantly inhibited S. aureus and C. albicans from forming biofilms and adhering to surfaces by 90–95% at concentrations between 0.025 and 0.1% w/v.
Antibiofilm activities were also demonstrated for BSs produced by probiotics of the genus Bacillus sp. that were isolated from cervicovaginal samples. This bioproduct, called BioSa3, was highly effective in the formation of biofilms of different pathogenic and multidrug-resistant strains, such as S. aureus and Staphylococcus haemolyticus. The anti-biofilm effect may be related to the ability of BioSa3 to alter the membrane physiology of the tested pathogens to cause a significant decrease in surface hydrophobicity [133].
Thus, SACs are good candidates for the emergence of new therapies to better control multidrug-resistant microorganisms and inhibit infections associated with biofilms, protecting surfaces from microbial contamination.

3.6. Wound Healing

Wound healing is an important but complicated process of tissue repair in humans or animals, comprising a multifaceted process organized by sequential and overlapping phases, including hemostasis, inflammation phase, proliferation phase, and remodeling phase [134,135]. Failure of one of these phases caused by a deregulated immune response or insufficient oxygenation impairs the healing process, leading to ulcerative skin defect (chronic wound) or excessive scar tissue formation (hypertrophic or keloid scarring) [136,137].
Treating wounds of different etiologies constitutes an important part of the total health budget, mostly affected by three important cost drivers: curing time, frequency of dressing change, and complications. Moreover, chronic wound infection, one of the leading causes of nonhealing, contributes significantly to rising healthcare costs. Although the treatment of an uncomplicated surgical incision is relatively inexpensive, the costs can increase significantly when infections occur [138].
Biofilms, commonly found in chronic wounds, contribute to infections, causing slower healing. Infections in chronic wounds are usually caused by multiple species [139], with P. aeruginosa and S. aureus being the most common. Although most microbial communities usually form on the wound’s outer layer, some biofilms are also embedded in deeper layers, such as P. aeruginosa biofilms, which are difficult to diagnose via traditional wound smear culture [140,141]. Moreover, antibiotic resistance of bacteria in biofilms is a crucial problem in the management and treatment of chronic wounds [139].
For these reasons, physicians and the scientific community consider the management and treatment of wounds, as well as biofilm prevention, a top priority. In this context, SACs recently emerged as promising agents that promote wound healing with low irritation and high compatibility with human skin [14]. Furthermore, these bioproducts promote fibroblast and epithelial cell proliferation, faster re-epithelialization, and collagen deposition, leading to a faster healing process [142,143].
Surfactin A from B. subtilis promotes wound healing and scar inhibition. During the healing process, it up-regulates the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor, accelerates keratinocyte migration via mitogen-activated protein kinase (MAPK), and factor nuclear-κB (NF-κB) signaling pathways and also regulates pro-inflammatory cytokine secretion and macrophage phenotypic exchange. Furthermore, surfactin A inhibits scar tissue formation by influencing α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-β) expression [144]. Therefore, the healing potency of the lipopeptides B. subtilis SPB1 is due to their antioxidant activity potential revealed in vitro [143].
A previously unknown lipopeptide 78 (LP78) from S. epidermidis inhibited TLR3-mediated skin inflammation and promoted wound healing. The skin lesion activated TLR3/NF-κB, promoting p65 and PPARγ interaction in the nuclei and initiating the inflammatory response in keratinocytes. Next, LP78 activated the TLR2-SRC, inducing β-catenin phosphorylation in Tyr. Phospho-β-catenin is translocated into the nuclei to bind to PPARγ, thereby interrupting the p65 and PPARγ interaction. Dissociation between p65 and PPARγ reduced TLR3-induced inflammatory cytokine expression in skin wounds of normal and diabetic mice, which correlated with faster wound healing [145].
As an alternative to improve this healing process, the formulation of nanolipopeptide biosurfactant (NLPB) from the lipopeptide biosurfactant (LPB) produced by Acinetobacter junii was reported as promising for performing healing activity. The percentage of wound closure of mice treated with NLPB hydrogels at 2 mg/mL was approximately 80% on day 7 and 100% on day 15. The NLPB hydrogel formulation showed better efficacy in wound closure and healing when compared to the control [146].
A BS of glycolipid nature, which was synthesized by Bacillus licheniformis SV1, showed good cytocompatibility and increased 3T3/NIH fibroblasts proliferation in vitro. A previous study showed that the application of BS ointment in a skin excision wound in rats promoted re-epithelialization, fibroblast cell proliferation, and faster collagen deposition, demonstrating its potential transdermal properties to improve skin wound healing [147].
A previous study administered an RL-containing ointment (5 g/L) on the back of Wistar mice after creating an excision wound. Histopathological results revealed a significant healing effect of RL, demonstrating increased wound closure, improved collagenases, and reduced inflammation (decreasing the level of TNF-α) without inducing skin irritation [84]. Dirhamnolipid treatment has been suggested for cutaneous scar therapy, demonstrating an antifibrotic function in rabbit ear hypertrophic scar models with a significant reduction in the scar elevation index, type I collagen fibers, and α-SMA expression [148].
A cell culture model has demonstrated the wound healing capacity of SLs by using an in vitro human dermal fibroblast model as a substitute for human skin, revealing that SLs affected the ability of human skin fibroblasts to express collagen I mRNA (Col-I) and elastase inhibition (IC50 = 38.5 μg/mL) [112]. In addition, Kwak et al. (2021), using an in vitro wound healing assay in human colorectal adenocarcinoma (HT-29) cell line, showed a significantly increased collagenase-1 expression (p < 0.05) 48 h after SL treatment. Moreover, all SL dosages significantly increased occludin and matrilysin-1 (MMP-7) expression [149].

3.7. Other Considerations

We also consider that there are SACs molecules obtained by chemical synthesis processes, such as ultrashort synthetic surface active (USSA) [150,151]. Some of these can be synthesized as C-terminal amides on Rink amide (4-Methylbenzhydrylamine (MBHA) resin using 9-fluorenylmethoxycarbonyl/t-butylcarbamate [151]. The fundamental difference of the USSA, as lipopeptoids (modified SAC) in relation to the natural ones, is their immunomodulatory capacity. As seen in mouse infection models, they reduce the exacerbation of the disease, even if not presenting direct antibacterial activity [151]. This characteristic would be a limiting activity, since many natural ones lead to a disturbance of biological membranes, with antifungal and antibacterial actions [151].
New possibilities can be obtained for the SACs, as transformation systems applying recombinant plasmids have been employed to substantially increase the productivity of microbial biosurfactants, e.g., the engineered strain Pseudozyma sp. SY16, which increases the production of mannosylerythritol lipids (MELs) by up to 31.5%, suggesting that genetic engineering can improve the industrial application of yeast [152].

4. Conclusions

The BS and BE surface-active compounds have drawn the attention of the scientific community as a new generation of products with high potential in the biomedical and pharmaceutical fields. Their use, whether alone or in combination with other antimicrobial or chemotherapeutic agents, opens paths for new strategies to prevent and combat infections caused by bacteria, fungi, and viruses, as well as the formation and proliferation of biofilms. Furthermore, new anticancer treatments and wound healing applications can be explored in future studies.
These molecules affect various biological activities, making them suitable candidates for use in new generations of agents in the biotechnological, biomedical, and pharmaceutical fields. However, it is necessary to investigate their applications, cost-effectiveness, and availability further.

Author Contributions

Conceptualization, J.A. and A.M.; writing—original draft preparation, J.A., J.M., D.S. (Douglas Silva), A.A., K.S., L.C., D.S. (Darlan Silva) and W.P.; writing—review and editing, J.M., M.S., L.S. and A.M.; visualization, L.S., M.S. and A.M.; supervision, A.M.; project administration, J.M. and A.M.; funding acquisition, A.M. All authors have read and agreed to the published version of the manuscript.

Funding

This study was financed in part by Fundação de Amparo à Pesquisa e o Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA, BD-01413/19); and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ, 434149/2018-7).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors would like to thank Hélio Euclides S. dos Santos and Marinaldo for technical assistance.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

ACE2angiotensin-converting enzyme 2
BEbioemulsifier
BSbiosurfactant
CD4differentiation cluster 4
CD25differentiation cluster 25
CD31differentiation cluster 31
COX-2cyclooxygenase-2
FOXP3Forkhead box protein P3
HIF-1αhypoxia-inducible factor-1α
HT-29human colorectal adenocarcinoma
IL-2interleukin 2
IL-10interleukin 10
IL1-1βinterleukin 10-1β
IL-8interleukin 8
IgEimmunoglobulin E
iNOSinducible nitric oxide synthase
LP78lipopeptide 78
MBHA(4-Methylbenzhydrylamine)
MAPKmitogen-activated protein kinase
MELsmannosylerythritol lipids
MICminimum inhibitory concentration
MICsminimum inhibitory concentrations
MRSAmethicillin-resistant S. aureus
NFκB factor nuclear-κB
NFκBp65- nuclear factor kappa- β p65
NLPBnanolipopeptide biosurfactant
NOnitric oxide
P-AktP-mitogen-activated
P-GSK3βprotein kinase syntoxic glycogen-3 beta
PPARγperoxisome proliferator-activated receptor γ
QSquorum sensing
RLrhamnolipid
SACssurface-active compounds
TGF-βtransforming growth factor
TLR3Toll-like receptor 3
TNF-αtumor necrosis factor α
USSAultrashort synthetic surface active
α-SMAinfluencing α-smooth muscle actin

References

  1. Franzetti, A.; Tamburini, E.; Banat, I.M. Applications of Biological Surface-Active Compounds in Remediation Technologies. Adv. Exp. Med. Biol. 2010, 672, 121–134. [Google Scholar] [CrossRef] [PubMed]
  2. Phulpoto, I.A.; Yu, Z.; Hu, B.; Wang, Y.; Ndayisenga, F.; Li, J.; Liang, H.; Qazi, M.A. Production and Characterization of Surfactin-like Biosurfactant Produced by Novel Strain Bacillus nealsonii S2MT and It’s Potential for Oil Contaminated Soil Remediation. Microb. Cell Fact. 2020, 19, 145. [Google Scholar] [CrossRef] [PubMed]
  3. Uzoigwe, C.; Burgess, J.G.; Ennis, C.J.; Rahman, P.K.S.M. Bioemulsifiers Are Not Biosurfactants and Require Different Screening Approaches. Front. Microbiol. 2015, 6, 245. [Google Scholar] [CrossRef] [PubMed]
  4. Durval, I.J.B.; Mendonça, A.H.R.; Rocha, I.V.; Luna, J.M.; Rufino, R.D.; Converti, A.; Sarubbo, L.A. Production, Characterization, Evaluation and Toxicity Assessment of a Bacillus cereus UCP 1615 Biosurfactant for Marine Oil Spills Bioremediation. Mar. Pollut. Bull. 2020, 157, 111357. [Google Scholar] [CrossRef]
  5. Ceresa, C.; Tessarolo, F.; Maniglio, D.; Tambone, E.; Carmagnola, I.; Fedeli, E.; Caola, I.; Nollo, G.; Chiono, V.; Allegrone, G.; et al. Medical-Grade Silicone Coated with Rhamnolipid R89 Is Effective against Staphylococcus spp. Biofilms. Molecules 2019, 24, 3843. [Google Scholar] [CrossRef]
  6. Md Badrul Hisham, N.H.; Ibrahim, M.F.; Ramli, N.; Abd-Aziz, S. Production of Biosurfactant Produced from Used Cooking Oil by Bacillus Sp. HIP3 for Heavy Metals Removal. Molecules 2019, 24, 2617. [Google Scholar] [CrossRef]
  7. Yamasaki, R.; Kawano, A.; Yoshioka, Y.; Ariyoshi, W. Rhamnolipids and Surfactin Inhibit the Growth or Formation of Oral Bacterial Biofilm. BMC Microbiol. 2020, 20, 358. [Google Scholar] [CrossRef]
  8. Sun, W.; Zhu, B.; Yang, F.; Dai, M.; Sehar, S.; Peng, C.; Ali, I.; Naz, I. Optimization of Biosurfactant Production from Pseudomonas sp. CQ2 and Its Application for Remediation of Heavy Metal Contaminated Soil. Chemosphere 2021, 265, 129090. [Google Scholar] [CrossRef]
  9. Sharma, D.; Misba, L.; Khan, A.U. Antibiotics versus Biofilm: An Emerging Battleground in Microbial Communities. Antimicrob. Resist. Infect. Control 2019, 8, 76. [Google Scholar] [CrossRef]
  10. Gaur, V.K.; Regar, R.K.; Dhiman, N.; Gautam, K.; Srivastava, J.K.; Patnaik, S.; Kamthan, M.; Manickam, N. Biosynthesis and Characterization of Sophorolipid Biosurfactant by Candida spp.: Application as Food Emulsifier and Antibacterial Agent. Bioresour. Technol. 2019, 285, 121314. [Google Scholar] [CrossRef]
  11. Kumari, A.; Kumari, S.; Prasad, G.S.; Pinnaka, A.K. Production of Sophorolipid Biosurfactant by Insect Derived Novel Yeast Metschnikowia churdharensis f.A., Sp. Nov., and Its Antifungal Activity against Plant and Human Pathogens. Front. Microbiol. 2021, 12, 678668. [Google Scholar] [CrossRef] [PubMed]
  12. Giugliano, R.; Buonocore, C.; Zannella, C.; Chianese, A.; Palma Esposito, F.; Tedesco, P.; De Filippis, A.; Galdiero, M.; Franci, G.; de Pascale, D. Antiviral Activity of the Rhamnolipids Mixture from the Antarctic Bacterium Pseudomonas gessardii M15 against Herpes simplex Viruses and Coronaviruses. Pharmaceutics 2021, 13, 2121. [Google Scholar] [CrossRef] [PubMed]
  13. Kim, H.-Y.; Jung, H.; Kim, H.-M.; Jeong, H.-J. Surfactin Exerts an Anti-Cancer Effect through Inducing Allergic Reactions in Melanoma Skin Cancer. Int. Immunopharmacol. 2021, 99, 107934. [Google Scholar] [CrossRef] [PubMed]
  14. Ceresa, C.; Fracchia, L.; Fedeli, E.; Porta, C.; Banat, I.M. Recent Advances in Biomedical, Therapeutic and Pharmaceutical Applications of Microbial Surfactants. Pharmaceutics 2021, 13, 466. [Google Scholar] [CrossRef]
  15. Mujumdar, S.; Joshi, P.; Karve, N. Production, Characterization, and Applications of Bioemulsifiers (BE) and Biosurfactants (BS) Produced by Acinetobacter Spp.: A Review. J. Basic Microbiol. 2019, 59, 277–287. [Google Scholar] [CrossRef]
  16. Cazals, F.; Huguenot, D.; Crampon, M.; Colombano, S.; Betelu, S.; Galopin, N.; Perrault, A.; Simonnot, M.-O.; Ignatiadis, I.; Rossano, S. Production of Biosurfactant Using the Endemic Bacterial Community of a PAHs Contaminated Soil, and Its Potential Use for PAHs Remobilization. Sci. Total Environ. 2020, 709, 136143. [Google Scholar] [CrossRef]
  17. Loeto, D.; Jongman, M.; Lekote, L.; Muzila, M.; Mokomane, M.; Motlhanka, K.; Ndlovu, T.; Zhou, N. Biosurfactant Production by Halophilic Yeasts Isolated from Extreme Environments in Botswana. FEMS Microbiol. Lett. 2021, 368, 146. [Google Scholar] [CrossRef]
  18. Silva, M.E.T.; Duvoisin, S., Jr.; Oliveira, R.L.; Banhos, E.F.; Souza, A.Q.L.; Albuquerque, P.M. Biosurfactant Production of Piper hispidum Endophytic Fungi. J. Appl. Microbiol. 2021, 130, 561–569. [Google Scholar] [CrossRef]
  19. Nayarisseri, A.; Singh, P.; Singh, S.K. Screening, Isolation and Characterization of Biosurfactant-Producing Bacillus tequilensis Strain ANSKLAB04 from Brackish River Water. Int. J. Environ. Sci. Technol. 2019, 16, 7103–7112. [Google Scholar] [CrossRef]
  20. Desai, J.D.; Banat, I.M. Microbial Production of Surfactants and Their Commercial Potential. Fuel Energy Abstr. 1997, 38, 221. [Google Scholar] [CrossRef]
  21. Chen, W.-C.; Juang, R.-S.; Wei, Y.-H. Applications of a Lipopeptide Biosurfactant, Surfactin, Produced by Microorganisms. Biochem. Eng. J. 2015, 103, 158–169. [Google Scholar] [CrossRef]
  22. Otzen, D.E. Biosurfactants and Surfactants Interacting with Membranes and Proteins: Same but Different? Biochim. Biophys. Acta 2017, 1859, 639–649. [Google Scholar] [CrossRef] [PubMed]
  23. Hogan, D.E.; Tian, F.; Malm, S.W.; Olivares, C.; Palos Pacheco, R.; Simonich, M.T.; Hunjan, A.S.; Tanguay, R.L.; Klimecki, W.T.; Polt, R.; et al. Biodegradability and Toxicity of Monorhamnolipid Biosurfactant Diastereomers. J. Hazard. Mater. 2019, 364, 600–607. [Google Scholar] [CrossRef]
  24. Qazi, M.A.; Wang, Q.; Dai, Z. Sophorolipids Bioproduction in the Yeast Starmerella bombicola: Current Trends and Perspectives. Bioresour. Technol. 2022, 346, 126593. [Google Scholar] [CrossRef]
  25. Ceresa, C.; Hutton, S.; Lajarin-Cuesta, M.; Heaton, R.; Hargreaves, I.; Fracchia, L.; De Rienzo, M.A.D. Production of Mannosylerythritol Lipids (MELs) to Be Used as Antimicrobial Agents against S. aureus ATCC 6538. Curr. Microbiol. 2020, 77, 1373–1380. [Google Scholar] [CrossRef] [PubMed]
  26. Niu, Y.; Wu, J.; Wang, W.; Chen, Q. Production and Characterization of a New Glycolipid, Mannosylerythritol Lipid, from Waste Cooking Oil Biotransformation by Pseudozyma aphidis ZJUDM34. Food Sci. Nutr. 2019, 7, 937–948. [Google Scholar] [CrossRef] [PubMed]
  27. Luong, T.M.; Ponamoreva, O.N.; Nechaeva, I.A.; Petrikov, K.V.; Delegan, Y.A.; Surin, A.K.; Linklater, D.; Filonov, A.E. Characterization of Biosurfactants Produced by the Oil-Degrading Bacterium Rhodococcus erythropolis S67 at Low Temperature. World J. Microbiol. Biotechnol. 2018, 34, 20. [Google Scholar] [CrossRef]
  28. Kubicki, S.; Bollinger, A.; Katzke, N.; Jaeger, K.-E.; Loeschcke, A.; Thies, S. Marine Biosurfactants: Biosynthesis, Structural Diversity and Biotechnological Applications. Mar. Drugs 2019, 17, 408. [Google Scholar] [CrossRef]
  29. Hu, F.; Liu, Y.; Li, S. Rational Strain Improvement for Surfactin Production: Enhancing the Yield and Generating Novel Structures. Microb. Cell Fact. 2019, 18, 42. [Google Scholar] [CrossRef]
  30. Habe, H.; Taira, T.; Sato, Y.; Imura, T.; Ano, T. Evaluation of Yield and Surface Tension-Lowering Activity of Iturin a Produced by Bacillus subtilis RB14. J. Oleo Sci. 2019, 68, 1157–1162. [Google Scholar] [CrossRef]
  31. Sarwar, A.; Brader, G.; Corretto, E.; Aleti, G.; Abaidullah, M.; Sessitsch, A.; Hafeez, F.Y. Qualitative Analysis of Biosurfactants from Bacillus Species Exhibiting Antifungal Activity. PLoS ONE 2018, 13, e0198107. [Google Scholar] [CrossRef]
  32. Denoirjean, T.; Doury, G.; Poli, P.; Coutte, F.; Ameline, A. Effects of Bacillus Lipopeptides on the Survival and Behavior of the Rosy Apple Aphid Dysaphis Plantaginea. Ecotoxicol. Environ. Saf. 2021, 226, 112840. [Google Scholar] [CrossRef] [PubMed]
  33. Singh, P.; Patil, Y.; Rale, V. Biosurfactant Production: Emerging Trends and Promising Strategies. J. Appl. Microbiol. 2019, 126, 2–13. [Google Scholar] [CrossRef]
  34. Zambry, N.S.; Rusly, N.S.; Awang, M.S.; Md Noh, N.A.; Yahya, A.R.M. Production of Lipopeptide Biosurfactant in Batch and Fed-Batch Streptomyces sp. PBD-410L Cultures Growing on Palm Oil. Bioprocess Biosyst. Eng. 2021, 44, 1577–1592. [Google Scholar] [CrossRef] [PubMed]
  35. Pardhi, D.S.; Panchal, R.R.; Raval, V.H.; Rajput, K.N. Statistical Optimization of Medium Components for Biosurfactant Production by Pseudomonas guguanensis D30. Prep. Biochem. Biotechnol. 2022, 52, 171–180. [Google Scholar] [CrossRef] [PubMed]
  36. Dos Santos, R.A.; Rodríguez, D.M.; Ferreira, I.N.d.S.; de Almeida, S.M.; Takaki, G.M.d.C.; de Lima, M.A.B. Novel Production of Biodispersant by Serratia marcescens UCP 1549 in Solid-State Fermentation and Application for Oil Spill Bioremediation. Environ. Technol. 2021, 43, 1–12. [Google Scholar] [CrossRef]
  37. Elkhawaga, M.A. Optimization and Characterization of Biosurfactant from Streptomyces griseoplanus NRRL-ISP5009 (MS1). J. Appl. Microbiol. 2018, 124, 691–707. [Google Scholar] [CrossRef]
  38. Bezza, F.A.; Chirwa, E.M.N. Biosurfactant-Enhanced Bioremediation of Aged Polycyclic Aromatic Hydrocarbons (PAHs) in Creosote Contaminated Soil. Chemosphere 2016, 144, 635–644. [Google Scholar] [CrossRef]
  39. Elakkiya, V.T.; SureshKumar, P.; Alharbi, N.S.; Kadaikunnan, S.; Khaled, J.M.; Govindarajan, M. Swift Production of Rhamnolipid Biosurfactant, Biopolymer and Synthesis of Biosurfactant-Wrapped Silver Nanoparticles and Its Enhanced Oil Recovery. Saudi J. Biol. Sci. 2020, 27, 1892–1899. [Google Scholar] [CrossRef]
  40. Nurfarahin, A.H.; Mohamed, M.S.; Phang, L.Y. Culture Medium Development for Microbial-Derived Surfactants Production-an Overview. Molecules 2018, 23, 1049. [Google Scholar] [CrossRef]
  41. Liu, J.-F.; Mbadinga, S.M.; Yang, S.-Z.; Gu, J.-D.; Mu, B.-Z. Chemical Structure, Property and Potential Applications of Biosurfactants Produced by Bacillus subtilis in Petroleum Recovery and Spill Mitigation. Int. J. Mol. Sci. 2015, 16, 4814–4837. [Google Scholar] [CrossRef] [PubMed]
  42. De Almeida, D.G.; Soares Da Silva, R.d.C.F.; Luna, J.M.; Rufino, R.D.; Santos, V.A.; Banat, I.M.; Sarubbo, L.A. Biosurfactants: Promising Molecules for Petroleum Biotechnology Advances. Front. Microbiol. 2016, 7, 1718. [Google Scholar] [CrossRef] [PubMed]
  43. Ostendorf, T.A.; Silva, I.A.; Converti, A.; Sarubbo, L.A. Production and Formulation of a New Low-Cost Biosurfactant to Remediate Oil-Contaminated Seawater. J. Biotechnol. 2019, 295, 71–79. [Google Scholar] [CrossRef] [PubMed]
  44. Silva, I.A.; Veras, B.O.; Ribeiro, B.G.; Aguiar, J.S.; Campos Guerra, J.M.; Luna, J.M.; Sarubbo, L.A. Production of Cupcake-like Dessert Containing Microbial Biosurfactant as an Emulsifier. PeerJ 2020, 8, e9064. [Google Scholar] [CrossRef]
  45. Ohadi, M.; Shahravan, A.; Dehghannoudeh, N.; Eslaminejad, T.; Banat, I.M.; Dehghannoudeh, G. Potential Use of Microbial Surfactant in Microemulsion Drug Delivery System: A Systematic Review. Drug Des. Dev. Ther. 2020, 14, 541–550. [Google Scholar] [CrossRef]
  46. Abdelli, F.; Jardak, M.; Elloumi, J.; Stien, D.; Cherif, S.; Mnif, S.; Aifa, S. Antibacterial, Anti-Adherent and Cytotoxic Activities of Surfactin(s) from a Lipolytic Strain Bacillus safensis F4. Biodegradation 2019, 30, 287–300. [Google Scholar] [CrossRef] [PubMed]
  47. Bhaumik, M.; Dhanarajan, G.; Chopra, J.; Kumar, R.; Hazra, C.; Sen, R. Production, Partial Purification and Characterization of a Proteoglycan Bioemulsifier from an Oleaginous Yeast. Bioprocess Biosyst. Eng. 2020, 43, 1747–1759. [Google Scholar] [CrossRef]
  48. Rosenberg, E.; Ron, E.Z. High- and Low-Molecular-Mass Microbial Surfactants. Appl. Microbiol. Biotechnol. 1999, 52, 154–162. [Google Scholar] [CrossRef]
  49. Ortega-de la Rosa, N.D.; Vázquez-Vázquez, J.L.; Huerta-Ochoa, S.; Gimeno, M.; Gutiérrez-Rojas, M. Stable Bioemulsifiers Are Produced by Acinetobacter bouvetii UAM25 Growing in Different Carbon Sources. Bioprocess Biosyst. Eng. 2018, 41, 859–869. [Google Scholar] [CrossRef]
  50. Patil, J.R.; Chopade, B.A. Studies on Bioemulsifier Production by Acinetobacter Strains Isolated from Healthy Human Skin. J. Appl. Microbiol. 2001, 91, 290–298. [Google Scholar] [CrossRef]
  51. Fan, Y.; Tao, W.; Huang, H.; Li, S. Characterization of a Novel Bioemulsifier from Pseudomonas stutzeri. World J. Microbiol. Biotechnol. 2017, 33, 161. [Google Scholar] [CrossRef] [PubMed]
  52. Adetunji, A.I.; Olaniran, A.O. Production and Characterization of Bioemulsifiers from Acinetobacter strains Isolated from Lipid-Rich Wastewater. 3 Biotech 2019, 9, 151. [Google Scholar] [CrossRef] [PubMed]
  53. Marques, N.S.A.A.; Silva, I.G.S.d.; Cavalcanti, D.L.; Maia, P.C.S.V.; Santos, V.P.; Andrade, R.F.S.; Campos-Takaki, G.M. Eco-Friendly Bioemulsifier Production by Mucor Circinelloides UCP0001 Isolated from Mangrove Sediments Using Renewable Substrates for Environmental Applications. Biomolecules 2020, 10, 365. [Google Scholar] [CrossRef] [PubMed]
  54. Gudiña, E.J.; Pereira, J.F.B.; Costa, R.; Evtuguin, D.V.; Coutinho, J.A.P.; Teixeira, J.A.; Rodrigues, L.R. Novel Bioemulsifier Produced by a Paenibacillus Strain Isolated from Crude Oil. Microb. Cell Fact. 2015, 14, 14. [Google Scholar] [CrossRef]
  55. Tao, W.; Lin, J.; Wang, W.; Huang, H.; Li, S. Designer Bioemulsifiers Based on Combinations of Different Polysaccharides with the Novel Emulsifying Esterase AXE from Bacillus Subtilis CICC 20034. Microb. Cell Fact. 2019, 18, 173. [Google Scholar] [CrossRef] [PubMed]
  56. Dastgheib, S.M.M.; Amoozegar, M.A.; Elahi, E.; Asad, S.; Banat, I.M. Bioemulsifier Production by a Halothermophilic Bacillus Strain with Potential Applications in Microbially Enhanced Oil Recovery. Biotechnol. Lett. 2008, 30, 263–270. [Google Scholar] [CrossRef]
  57. Goldman, S.; Shabtai, Y.; Rubinovitz, C.; Rosenberg, E.; Gutnick, D.L. Emulsan in Acinetobacter calcoaceticus RAG-1: Distribution of Cell-Free and Cell-Associated Cross-Reacting Material. Appl. Environ. Microbiol. 1982, 44, 165–170. [Google Scholar] [CrossRef]
  58. Toren, A.; Navon-Venezia, S.; Ron, E.Z.; Rosenberg, E. Emulsifying Activities of Purified Alasan Proteins from Acinetobacter radioresistens KA53. Appl. Environ. Microbiol. 2001, 67, 1102–1106. [Google Scholar] [CrossRef]
  59. Ohadi, M.; Dehghannoudeh, G.; Forootanfar, H.; Shakibaie, M.; Rajaee, M. Investigation of the Structural, Physicochemical Properties, and Aggregation Behavior of Lipopeptide Biosurfactant Produced by Acinetobacter junii B6. Int. J. Biol. Macromol. 2018, 112, 712–719. [Google Scholar] [CrossRef]
  60. Dong, H.; Xia, W.; Dong, H.; She, Y.; Zhu, P.; Liang, K.; Zhang, Z.; Liang, C.; Song, Z.; Sun, S.; et al. Rhamnolipids Produced by Indigenous Acinetobacter junii from Petroleum Reservoir and Its Potential in Enhanced Oil Recovery. Front. Microbiol. 2016, 7, 1710. [Google Scholar] [CrossRef]
  61. Rosenberg, E.; Rubinovitz, C.; Gottlieb, A.; Rosenhak, S.; Ron, E.Z. Production of Biodispersan by Acinetobacter calcoaceticus A2. Appl. Environ. Microbiol. 1988, 54, 317–322. [Google Scholar] [CrossRef] [PubMed]
  62. Klausmann, P.; Hennemann, K.; Hoffmann, M.; Treinen, C.; Aschern, M.; Lilge, L.; Morabbi Heravi, K.; Henkel, M.; Hausmann, R. Bacillus subtilis High Cell Density Fermentation Using a Sporulation-Deficient Strain for the Production of Surfactin. Appl. Microbiol. Biotechnol. 2021, 105, 4141–4151. [Google Scholar] [CrossRef] [PubMed]
  63. Díaz De Rienzo, M.A.; Kamalanathan, I.D.; Martin, P.J. Comparative Study of the Production of Rhamnolipid Biosurfactants by B. thailandensis E264 and P. aeruginosa ATCC 9027 Using Foam Fractionation. Process Biochem. 2016, 51, 820–827. [Google Scholar] [CrossRef]
  64. Kim, Y.T.; Kim, S.E.; Lee, W.J.; Fumei, Z.; Cho, M.S.; Moon, J.S.; Oh, H.-W.; Park, H.-Y.; Kim, S.U. Isolation and Characterization of a High Iturin Yielding Bacillus Velezensis UV Mutant with Improved Antifungal Activity. PLoS ONE 2020, 15, e0234177. [Google Scholar] [CrossRef]
  65. Ganji, Z.; Beheshti-Maal, K.; Massah, A.; Emami-Karvani, Z. A Novel Sophorolipid-Producing Candida keroseneae GBME-IAUF-2 as a Potential Agent in Microbial Enhanced Oil Recovery (MEOR). FEMS Microbiol. Lett. 2020, 367, fnaa144. [Google Scholar] [CrossRef]
  66. Rufino, R.D.; Luna, J.M.; Sarubbo, L.A.; Rodrigues, L.R.M.; Teixeira, J.A.C.; Campos-Takaki, G.M. Antimicrobial and Anti-Adhesive Potential of a Biosurfactant Rufisan Produced by Candida lipolytica UCP 0988. Colloids Surf. B Biointerfaces 2011, 84, 1–5. [Google Scholar] [CrossRef]
  67. Nelson, J.; El-Gendy, A.O.; Mansy, M.S.; Ramadan, M.A.; Aziz, R.K. The Biosurfactants Iturin, Lichenysin and Surfactin, from Vaginally Isolated Lactobacilli, Prevent Biofilm Formation by Pathogenic Candida. FEMS Microbiol. Lett. 2020, 367, fnaa126. [Google Scholar] [CrossRef]
  68. Zhao, F.; Han, S.; Zhang, Y. Comparative Studies on the Structural Composition, Surface/Interface Activity and Application Potential of Rhamnolipids Produced by Pseudomonas aeruginosa Using Hydrophobic or Hydrophilic Substrates. Bioresour. Technol. 2020, 295, 122269. [Google Scholar] [CrossRef] [PubMed]
  69. Bonnichsen, L.; Bygvraa Svenningsen, N.; Rybtke, M.; de Bruijn, I.; Raaijmakers, J.M.; Tolker-Nielsen, T.; Nybroe, O. Lipopeptide Biosurfactant Viscosin Enhances Dispersal of Pseudomonas fluorescens SBW25 Biofilms. Microbiology 2015, 161, 2289–2297. [Google Scholar] [CrossRef]
  70. Phulpoto, I.A.; Wang, Y.; Qazi, M.A.; Hu, B.; Ndayisenga, F.; Yu, Z. Bioprospecting of Rhamnolipids Production and Optimization by an Oil-Degrading Pseudomonas sp. S2WE Isolated from Freshwater Lake. Bioresour. Technol. 2021, 323, 124601. [Google Scholar] [CrossRef]
  71. Hu, X.; Cheng, T.; Liu, J. A Novel Serratia Sp. ZS6 Isolate Derived from Petroleum Sludge Secretes Biosurfactant and Lipase in Medium with Olive Oil as Sole Carbon Source. AMB Express 2018, 8, 165. [Google Scholar] [CrossRef] [PubMed]
  72. Amaral, P.F.F.; da Silva, J.M.; Lehocky, M.; Barros-Timmons, A.M.V.; Coelho, M.A.Z.; Marrucho, I.M.; Coutinho, J.A.P. Production and Characterization of a Bioemulsifier from Yarrowia lipolytica. Process Biochem. 2006, 41, 1894–1898. [Google Scholar] [CrossRef]
  73. de Souza Monteiro, A.; Domingues, V.S.; Souza, M.V.; Lula, I.; Gonçalves, D.B.; de Siqueira, E.P.; Dos Santos, V.L. Bioconversion of Biodiesel Refinery Waste in the Bioemulsifier by Trichosporon Mycotoxinivorans CLA2. Biotechnol. Biofuels 2012, 5, 29. [Google Scholar] [CrossRef] [PubMed]
  74. Anestopoulos, I.; Kiousi, D.E.; Klavaris, A.; Galanis, A.; Salek, K.; Euston, S.R.; Pappa, A.; Panayiotidis, M.I. Surface Active Agents and Their Health-Promoting Properties: Molecules of Multifunctional Significance. Pharmaceutics 2020, 12, 688. [Google Scholar] [CrossRef]
  75. Lerminiaux, N.A.; Cameron, A.D.S. Horizontal Transfer of Antibiotic Resistance Genes in Clinical Environments. Can. J. Microbiol. 2019, 65, 34–44. [Google Scholar] [CrossRef]
  76. Melnyk, A.H.; Wong, A.; Kassen, R. The Fitness Costs of Antibiotic Resistance Mutations. Evol. Appl. 2015, 8, 273–283. [Google Scholar] [CrossRef]
  77. Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet, D.L.; Pulcini, C.; Kahlmeter, G.; Kluytmans, J.; Carmeli, Y.; et al. WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018, 18, 318–327. [Google Scholar] [CrossRef]
  78. Colombo, A.L.; Júnior, J.N.d.A.; Guinea, J. Emerging Multidrug-Resistant Candida Species. Curr. Opin. Infect. Dis. 2017, 30, 528–538. [Google Scholar] [CrossRef]
  79. Kean, R.; Ramage, G. Combined Antifungal Resistance and Biofilm Tolerance: The Global Threat of Candida Auris. mSphere 2019, 4, e00458-19. [Google Scholar] [CrossRef]
  80. Kumar, A.; Nair, R.; Kumar, M.; Banerjee, A.; Chakrabarti, A.; Rudramurthy, S.M.; Bagga, R.; Gaur, N.A.; Mondal, A.K.; Prasad, R. Assessment of Antifungal Resistance and Associated Molecular Mechanism in Candida albicans Isolates from Different Cohorts of Patients in North Indian State of Haryana. Folia Microbiol. 2020, 65, 747–754. [Google Scholar] [CrossRef]
  81. Anestopoulos, I.; Kiousi, D.-E.; Klavaris, A.; Maijo, M.; Serpico, A.; Suarez, A.; Sanchez, G.; Salek, K.; Chasapi, S.A.; Zompra, A.A.; et al. Marine-Derived Surface Active Agents: Health-Promoting Properties and Blue Biotechnology-Based Applications. Biomolecules 2020, 10, 885. [Google Scholar] [CrossRef] [PubMed]
  82. Zhou, C.; Wang, F.; Chen, H.; Li, M.; Qiao, F.; Liu, Z.; Hou, Y.; Wu, C.; Fan, Y.; Liu, L.; et al. Selective Antimicrobial Activities and Action Mechanism of Micelles Self-Assembled by Cationic Oligomeric Surfactants. ACS Appl. Mater. Interfaces 2016, 8, 4242–4249. [Google Scholar] [CrossRef] [PubMed]
  83. Labena, A.; Hegazy, M.A.; Sami, R.M.; Hozzein, W.N. Multiple Applications of a Novel Cationic Gemini Surfactant: Anti-Microbial, Anti-Biofilm, Biocide, Salinity Corrosion Inhibitor, and Biofilm Dispersion (Part II). Molecules 2020, 25, 1348. [Google Scholar] [CrossRef] [PubMed]
  84. Sana, S.; Datta, S.; Biswas, D.; Sengupta, D. Assessment of Synergistic Antibacterial Activity of Combined Biosurfactants Revealed by Bacterial Cell Envelop Damage. Biochim. Biophys. Acta Biomembr. 2018, 1860, 579–585. [Google Scholar] [CrossRef]
  85. Naughton, P.J.; Marchant, R.; Naughton, V.; Banat, I.M. Microbial Biosurfactants: Current Trends and Applications in Agricultural and Biomedical Industries. J. Appl. Microbiol. 2019, 127, 12–28. [Google Scholar] [CrossRef] [PubMed]
  86. Haba, E.; Bouhdid, S.; Torrego-Solana, N.; Marqués, A.M.; Espuny, M.J.; García-Celma, M.J.; Manresa, A. Rhamnolipids as Emulsifying Agents for Essential Oil Formulations: Antimicrobial Effect against Candida albicans and Methicillin-Resistant Staphylococcus aureus. Int. J. Pharm. 2014, 476, 134–141. [Google Scholar] [CrossRef]
  87. Kurtzman, C.P.; Price, N.P.J.; Ray, K.J.; Kuo, T.-M. Production of Sophorolipid Biosurfactants by Multiple Species of the Starmerella (Candida) bombicola Yeast Clade: Sophorolipids from Yeasts. FEMS Microbiol. Lett. 2010, 311, 140–146. [Google Scholar] [CrossRef]
  88. Callaghan, B.; Lydon, H.; Roelants, S.L.K.W.; Van Bogaert, I.N.A.; Marchant, R.; Banat, I.M.; Mitchell, C.A. Lactonic Sophorolipids Increase Tumor Burden in Apcmin+/− Mice. PLoS ONE 2016, 11, e0156845. [Google Scholar] [CrossRef]
  89. Van Bogaert, I.N.A.; Zhang, J.; Soetaert, W. Microbial Synthesis of Sophorolipids. Process Biochem. 2011, 46, 821–833. [Google Scholar] [CrossRef]
  90. Sen, S.; Borah, S.N.; Bora, A.; Deka, S. Production, Characterization, and Antifungal Activity of a Biosurfactant Produced by Rhodotorula Babjevae YS3. Microb. Cell Fact. 2017, 16, 95. [Google Scholar] [CrossRef]
  91. Chen, M.; Wang, J.; Liu, B.; Zhu, Y.; Xiao, R.; Yang, W.; Ge, C.; Chen, Z. Biocontrol of Tomato Bacterial Wilt by the New Strain Bacillus velezensis FJAT-46737 and Its Lipopeptides. BMC Microbiol. 2020, 20, 160. [Google Scholar] [CrossRef] [PubMed]
  92. Wu, S.; Liu, G.; Zhou, S.; Sha, Z.; Sun, C. Characterization of Antifungal Lipopeptide Biosurfactants Produced by Marine Bacterium Bacillus Sp. CS30. Mar. Drugs 2019, 17, 199. [Google Scholar] [CrossRef] [PubMed]
  93. Perez, K.J.; Viana, J.D.S.; Lopes, F.C.; Pereira, J.Q.; Dos Santos, D.M.; Oliveira, J.S.; Velho, R.V.; Crispim, S.M.; Nicoli, J.R.; Brandelli, A.; et al. Bacillus Spp. Isolated from Puba as a Source of Biosurfactants and Antimicrobial Lipopeptides. Front. Microbiol. 2017, 8, 61. [Google Scholar] [CrossRef] [PubMed]
  94. Liu, J.; Li, W.; Zhu, X.; Zhao, H.; Lu, Y.; Zhang, C.; Lu, Z. Surfactin Effectively Inhibits Staphylococcus aureus Adhesion and Biofilm Formation on Surfaces. Appl. Microbiol. Biotechnol. 2019, 103, 4565–4574. [Google Scholar] [CrossRef]
  95. Ohadi, M.; Forootanfar, H.; Dehghannoudeh, G.; Eslaminejad, T.; Ameri, A.; Shakibaie, M.; Adeli-Sardou, M. Antimicrobial, Anti-Biofilm, and Anti-Proliferative Activities of Lipopeptide Biosurfactant Produced by Acinetobacter junii B6. Microb. Pathog. 2020, 138, 103806. [Google Scholar] [CrossRef] [PubMed]
  96. Mouafo, T.H.; Mbawala, A.; Ndjouenkeu, R. Effect of Different Carbon Sources on Biosurfactants’ Production by Three Strains of Lactobacillus spp. Biomed Res. Int. 2018, 2018, 5034783. [Google Scholar] [CrossRef]
  97. Liu, Y.; Ding, S.; Dietrich, R.; Märtlbauer, E.; Zhu, K. A Biosurfactant-Inspired Heptapeptide with Improved Specificity to Kill MRSA. Angew. Chem. Int. Ed. Engl. 2017, 56, 1486–1490. [Google Scholar] [CrossRef]
  98. Vollenbroich, D.; Ozel, M.; Vater, J.; Kamp, R.M.; Pauli, G. Mechanism of Inactivation of Enveloped Viruses by the Biosurfactant Surfactin from Bacillus subtilis. Biologicals 1997, 25, 289–297. [Google Scholar] [CrossRef]
  99. Yuan, L.; Zhang, S.; Wang, Y.; Li, Y.; Wang, X.; Yang, Q. Surfactin Inhibits Membrane Fusion during Invasion of Epithelial Cells by Enveloped Viruses. J. Virol. 2018, 92, e00809-18. [Google Scholar] [CrossRef]
  100. Wu, W.; Wang, J.; Lin, D.; Chen, L.; Xie, X.; Shen, X.; Yang, Q.; Wu, Q.; Yang, J.; He, J.; et al. Super Short Membrane-Active Lipopeptides Inhibiting the Entry of Influenza A Virus. Biochim. Biophys. Acta 2015, 1848, 2344–2350. [Google Scholar] [CrossRef]
  101. Chowdhury, T.; Baindara, P.; Mandal, S.M. LPD-12: A Promising Lipopeptide to Control COVID-19. Int. J. Antimicrob. Agents 2021, 57, 106218. [Google Scholar] [CrossRef] [PubMed]
  102. Outlaw, V.K.; Bovier, F.T.; Mears, M.C.; Cajimat, M.N.; Zhu, Y.; Lin, M.J.; Addetia, A.; Lieberman, N.A.P.; Peddu, V.; Xie, X.; et al. Inhibition of Coronavirus Entry in vitro and ex vivo by a Lipid-Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain. MBio 2020, 11, e01935-20. [Google Scholar] [CrossRef] [PubMed]
  103. Subramaniam, M.D.; Venkatesan, D.; Iyer, M.; Subbarayan, S.; Govindasami, V.; Roy, A.; Narayanasamy, A.; Kamalakannan, S.; Gopalakrishnan, A.V.; Thangarasu, R.; et al. Biosurfactants and Anti-Inflammatory Activity: A Potential New Approach towards COVID-19. Curr. Opin. Environ. Sci. Health 2020, 17, 72–81. [Google Scholar] [CrossRef] [PubMed]
  104. Shah, V.; Doncel, G.F.; Seyoum, T.; Eaton, K.M.; Zalenskaya, I.; Hagver, R.; Azim, A.; Gross, R. Sophorolipids, Microbial Glycolipids with Anti-Human Immunodeficiency Virus and Sperm-Immobilizing Activities. Antimicrob. Agents Chemother. 2005, 49, 4093–4100. [Google Scholar] [CrossRef] [PubMed]
  105. Borsanyiova, M.; Patil, A.; Mukherji, R.; Prabhune, A.; Bopegamage, S. Biological Activity of Sophorolipids and Their Possible Use as Antiviral Agents. Folia Microbiol. 2016, 61, 85–89. [Google Scholar] [CrossRef]
  106. Remichkova, M.; Galabova, D.; Roeva, I.; Karpenko, E.; Shulga, A.; Galabov, A.S. Anti-Herpesvirus Activities of Pseudomonas sp. S-17 Rhamnolipid and Its Complex with Alginate. Z. Naturforsch. C 2008, 63, 75–81. [Google Scholar] [CrossRef]
  107. Lozach, P.-Y. Cell Biology of Viral Infections. Cells 2020, 9, 2431. [Google Scholar] [CrossRef]
  108. Abdulkhaleq, L.A.; Assi, M.A.; Abdullah, R.; Zamri-Saad, M.; Taufiq-Yap, Y.H.; Hezmee, M.N.M. The Crucial Roles of Inflammatory Mediators in Inflammation: A Review. Vet. World 2018, 11, 627–635. [Google Scholar] [CrossRef]
  109. Wang, Y.; Tian, J.; Shi, F.; Li, X.; Hu, Z.; Chu, J. Protective Effect of Surfactin on Copper Sulfate-Induced Inflammation, Oxidative Stress, and Hepatic Injury in Zebrafish. Microbiol. Immunol. 2021, 65, 410–421. [Google Scholar] [CrossRef]
  110. Gan, P.; Jin, D.; Zhao, X.; Gao, Z.; Wang, S.; Du, P.; Qi, G. Bacillus-Produced Surfactin Attenuates Chronic Inflammation in Atherosclerotic Lesions of ApoE(−/−) Mice. Int. Immunopharmacol. 2016, 35, 226–234. [Google Scholar] [CrossRef]
  111. Xu, W.; Liu, H.; Wang, X.; Yang, Q. Surfactin Induces Maturation of Dendritic Cells in Vitro. Biosci. Rep. 2016, 36, e00387. [Google Scholar] [CrossRef] [PubMed]
  112. Maeng, Y.; Kim, K.T.; Zhou, X.; Jin, L.; Kim, K.S.; Kim, Y.H.; Lee, S.; Park, J.H.; Chen, X.; Kong, M.; et al. A Novel Microbial Technique for Producing High-Quality Sophorolipids from Horse Oil Suitable for Cosmetic Applications. Microb. Biotechnol. 2018, 11, 917–929. [Google Scholar] [CrossRef] [PubMed]
  113. Hagler, M.; Smith-Norowitz, T.A.; Chice, S.; Wallner, S.R.; Viterbo, D.; Mueller, C.M.; Gross, R.; Nowakowski, M.; Schulze, R.; Zenilman, M.E.; et al. Sophorolipids Decrease IgE Production in U266 Cells by Downregulation of BSAP (Pax5), TLR-2, STAT3 and IL-6. J. Allergy Clin. Immunol. 2007, 119, S263. [Google Scholar] [CrossRef]
  114. Hardin, R.; Pierre, J.; Schulze, R.; Mueller, C.M.; Fu, S.L.; Wallner, S.R.; Stanek, A.; Shah, V.; Gross, R.A.; Weedon, J.; et al. Sophorolipids Improve Sepsis Survival: Effects of Dosing and Derivatives. J. Surg. Res. 2007, 142, 314–319. [Google Scholar] [CrossRef]
  115. Mueller, C.M.; Lin, Y.-Y.; Viterbo, D.; Pierre, J.; Murray, S.A.; Shah, V.; Gross, R.; Schulze, R.; Zenilman, M.E.; Bluth, M.H. Sophorolipid Treatment Decreases Inflammatory Cytokine Expression in an in Vitro Model of Experimental Sepsis. FASEB J. 2006, 20, A204. [Google Scholar] [CrossRef]
  116. Kuyukina, M.S.; Ivshina, I.B.; Gein, S.V.; Baeva, T.A.; Chereshnev, V.A. In Vitro Immunomodulating Activity of Biosurfactant Glycolipid Complex from Rhodococcus ruber. Bull. Exp. Biol. Med. 2007, 144, 326–330. [Google Scholar] [CrossRef]
  117. Thakur, P.; Saini, N.K.; Thakur, V.K.; Gupta, V.K.; Saini, R.V.; Saini, A.K. Rhamnolipid the Glycolipid Biosurfactant: Emerging Trends and Promising Strategies in the Field of Biotechnology and Biomedicine. Microb. Cell Fact. 2021, 20, 1. [Google Scholar] [CrossRef]
  118. Rahimi, K.; Lotfabad, T.B.; Jabeen, F.; Mohammad Ganji, S. Cytotoxic Effects of Mono- and Di-Rhamnolipids from Pseudomonas aeruginosa MR01 on MCF-7 Human Breast Cancer Cells. Colloids Surf. B Biointerfaces 2019, 181, 943–952. [Google Scholar] [CrossRef]
  119. Ribeiro, I.A.C.; Faustino, C.M.C.; Guerreiro, P.S.; Frade, R.F.M.; Bronze, M.R.; Castro, M.F.; Ribeiro, M.H.L. Development of Novel Sophorolipids with Improved Cytotoxic Activity toward MDA-MB-231 Breast Cancer Cells: Development of Novel Sophorolipids With Cytotoxic Activity. J. Mol. Recognit. 2015, 28, 155–165. [Google Scholar] [CrossRef]
  120. Chen, J.; Song, X.; Zhang, H.; Qu, Y. Production, Structure Elucidation and Anticancer Properties of Sophorolipid from Wickerhamiella Domercqiae. Enzyme Microb. Technol. 2006, 39, 501–506. [Google Scholar] [CrossRef]
  121. Dey, G.; Bharti, R.; Dhanarajan, G.; Das, S.; Dey, K.K.; Kumar, B.N.P.; Sen, R.; Mandal, M. Marine Lipopeptide Iturin a Inhibits Akt Mediated GSK3β and FoxO3a Signaling and Triggers Apoptosis in Breast Cancer. Sci. Rep. 2015, 5, 10316. [Google Scholar] [CrossRef] [PubMed]
  122. Yan, J.; Bassler, B.L. Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial Biofilms. Cell Host Microbe 2019, 26, 15–21. [Google Scholar] [CrossRef] [PubMed]
  123. Roy, R.; Tiwari, M.; Donelli, G.; Tiwari, V. Strategies for Combating Bacterial Biofilms: A Focus on Anti-Biofilm Agents and Their Mechanisms of Action. Virulence 2018, 9, 522–554. [Google Scholar] [CrossRef] [PubMed]
  124. Rivardo, F.; Martinotti, M.G.; Turner, R.J.; Ceri, H. Synergistic Effect of Lipopeptide Biosurfactant with Antibiotics against Escherichia coli CFT073 Biofilm. Int. J. Antimicrob. Agents 2011, 37, 324–331. [Google Scholar] [CrossRef]
  125. Ceresa, C.; Rinaldi, M.; Fracchia, L. Synergistic Activity of Antifungal Drugs and Lipopeptide AC7 against Candida albicans Biofilm on Silicone. AIMS Bioeng. 2017, 4, 318–334. [Google Scholar] [CrossRef]
  126. Cordeiro, R.d.A.; Weslley Caracas Cedro, E.; Raquel Colares Andrade, A.; Serpa, R.; José de Jesus Evangelista, A.; Sales de Oliveira, J.; Santos Pereira, V.; Pereira Alencar, L.; Bruna Leite Mendes, P.; Cibelle Soares Farias, B.; et al. Inhibitory Effect of a Lipopeptide Biosurfactant Produced by Bacillus subtilis on Planktonic and Sessile Cells of Trichosporon spp. Biofouling 2018, 34, 309–319. [Google Scholar] [CrossRef]
  127. Da Silva, G.O.; Farias, B.C.S.; da Silva, R.B.; Teixeira, E.H.; Cordeiro, R.d.A.; Hissa, D.C.; Melo, V.M.M. Effects of Lipopeptide Biosurfactants on Clinical Strains of Malassezia furfur Growth and Biofilm Formation. Med. Mycol. 2021, 59, 1191–1201. [Google Scholar] [CrossRef]
  128. Allegrone, G.; Ceresa, C.; Rinaldi, M.; Fracchia, L. Diverse Effects of Natural and Synthetic Surfactants on the Inhibition of Staphylococcus aureus Biofilm. Pharmaceutics 2021, 13, 1172. [Google Scholar] [CrossRef]
  129. Shen, Y.; Li, P.; Chen, X.; Zou, Y.; Li, H.; Yuan, G.; Hu, H. Activity of Sodium Lauryl Sulfate, Rhamnolipids, and N-Acetylcysteine against Biofilms of Five Common Pathogens. Microb. Drug Resist. 2020, 26, 290–299. [Google Scholar] [CrossRef]
  130. Sidrim, J.J.; Ocadaque, C.J.; Amando, B.R.; de Guedes, G.M.; Costa, C.L.; Brilhante, R.S.; de Cordeiro, A.R.; Rocha, M.F.; Scm Castelo-Branco, D. Rhamnolipid Enhances Burkholderia pseudomallei Biofilm Susceptibility, Disassembly and Production of Virulence Factors. Future Microbiol. 2020, 15, 1109–1121. [Google Scholar] [CrossRef]
  131. Sen, S.; Borah, S.N.; Bora, A.; Deka, S. Rhamnolipid Exhibits Anti-Biofilm Activity against the Dermatophytic Fungi Trichophyton Rubrum and Trichophyton mentagrophytes. Biotechnol. Rep. 2020, 27, e00516. [Google Scholar] [CrossRef] [PubMed]
  132. Ceresa, C.; Fracchia, L.; Williams, M.; Banat, I.M.; Díaz De Rienzo, M.A. The Effect of Sophorolipids against Microbial Biofilms on Medical-Grade Silicone. J. Biotechnol. 2020, 309, 34–43. [Google Scholar] [CrossRef] [PubMed]
  133. Haddaji, N.; Ncib, K.; Bahia, W.; Ghorbel, M.; Leban, N.; Bouali, N.; Bechambi, O.; Mzoughi, R.; Mahdhi, A. Control of Multidrug-Resistant Pathogenic Staphylococci Associated with Vaginal Infection Using Biosurfactants Derived from Potential Probiotic Bacillus Strain. Fermentation 2022, 8, 19. [Google Scholar] [CrossRef]
  134. Wang, P.-H.; Huang, B.-S.; Horng, H.-C.; Yeh, C.-C.; Chen, Y.-J. Wound Healing. J. Chin. Med. Assoc. 2018, 81, 94–101. [Google Scholar] [CrossRef]
  135. Martin, P.; Nunan, R. Cellular and Molecular Mechanisms of Repair in Acute and Chronic Wound Healing. Br. J. Dermatol. 2015, 173, 370–378. [Google Scholar] [CrossRef] [PubMed]
  136. Tatara, A.M.; Kontoyiannis, D.P.; Mikos, A.G. Drug Delivery and Tissue Engineering to Promote Wound Healing in the Immunocompromised Host: Current Challenges and Future Directions. Adv. Drug Deliv. Rev. 2018, 129, 319–329. [Google Scholar] [CrossRef] [PubMed]
  137. Yip, W.L. Influence of Oxygen on Wound Healing: Oxygen and Wound Healing. Int. Wound J. 2015, 12, 620–624. [Google Scholar] [CrossRef]
  138. Lindholm, C.; Searle, R. Wound Management for the 21st Century: Combining Effectiveness and Efficiency: Wound Management for the 21st Century. Int. Wound J. 2016, 13 (Suppl. 2), 5–15. [Google Scholar] [CrossRef]
  139. Rahim, K.; Saleha, S.; Zhu, X.; Huo, L.; Basit, A.; Franco, O.L. Bacterial Contribution in Chronicity of Wounds. Microb. Ecol. 2017, 73, 710–721. [Google Scholar] [CrossRef]
  140. Pastar, I.; Nusbaum, A.G.; Gil, J.; Patel, S.B.; Chen, J.; Valdes, J.; Stojadinovic, O.; Plano, L.R.; Tomic-Canic, M.; Davis, S.C. Interactions of Methicillin Resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in Polymicrobial Wound Infection. PLoS ONE 2013, 8, e56846. [Google Scholar] [CrossRef]
  141. Banu, A.; Noorul Hassan, M.M.; Rajkumar, J.; Srinivasa, S. Spectrum of Bacteria Associated with Diabetic Foot Ulcer and Biofilm Formation: A Prospective Study. Aust. Med. J. 2015, 8, 280–285. [Google Scholar] [CrossRef] [PubMed]
  142. Ohadi, M.; Forootanfar, H.; Rahimi, H.R.; Jafari, E.; Shakibaie, M.; Eslaminejad, T.; Dehghannoudeh, G. Antioxidant Potential and Wound Healing Activity of Biosurfactant Produced by Acinetobacter junii B6. Curr. Pharm. Biotechnol. 2017, 18, 900–908. [Google Scholar] [CrossRef]
  143. Zouari, R.; Moalla-Rekik, D.; Sahnoun, Z.; Rebai, T.; Ellouze-Chaabouni, S.; Ghribi-Aydi, D. Evaluation of Dermal Wound Healing and in vitro Antioxidant Efficiency of Bacillus Subtilis SPB1 Biosurfactant. Biomed. Pharmacother. 2016, 84, 878–891. [Google Scholar] [CrossRef] [PubMed]
  144. Yan, L.; Liu, G.; Zhao, B.; Pang, B.; Wu, W.; Ai, C.; Zhao, X.; Wang, X.; Jiang, C.; Shao, D.; et al. Novel Biomedical Functions of Surfactin A from Bacillus subtilis in Wound Healing Promotion and Scar Inhibition. J. Agric. Food Chem. 2020, 68, 6987–6997. [Google Scholar] [CrossRef] [PubMed]
  145. Li, D.; Wang, W.; Wu, Y.; Ma, X.; Zhou, W.; Lai, Y. Lipopeptide 78 from Staphylococcus epidermidis Activates β-Catenin to Inhibit Skin Inflammation. J. Immunol. 2019, 202, 1219–1228. [Google Scholar] [CrossRef] [PubMed]
  146. Afsharipour, S.; Asadi, A.; Ohadi, M.; Ranjbar, M.; Forootanfar, H.; Jafari, E.; Dehghannoudeh, G. Preparation and Characterization of Nano-Lipopeptide Biosurfactant Hydrogel and Evaluation of Wound-Healing Properties. Bionanoscience 2021, 11, 1061–1069. [Google Scholar] [CrossRef]
  147. Gupta, S.; Raghuwanshi, N.; Varshney, R.; Banat, I.M.; Srivastava, A.K.; Pruthi, P.A.; Pruthi, V. Accelerated in Vivo Wound Healing Evaluation of Microbial Glycolipid Containing Ointment as a Transdermal Substitute. Biomed. Pharmacother. 2017, 94, 1186–1196. [Google Scholar] [CrossRef]
  148. Shen, C.; Jiang, L.; Shao, H.; You, C.; Zhang, G.; Ding, S.; Bian, T.; Han, C.; Meng, Q. Targeted Killing of Myofibroblasts by Biosurfactant Di-Rhamnolipid Suggests a Therapy against Scar Formation. Sci. Rep. 2016, 6, 37553. [Google Scholar] [CrossRef]
  149. Kwak, M.-J.; Park, M.-Y.; Kim, J.; Lee, H.; Whang, K.-Y. Curative Effects of Sophorolipid on Physical Wounds: In Vitro and in Vivo Studies. Vet. Med. Sci. 2021, 7, 1400–1408. [Google Scholar] [CrossRef]
  150. Domalaon, R.; Findlay, B.; Ogunsina, M.; Arthur, G.; Schweizer, F. Ultrashort cationic lipopeptides and lipopeptoids: Evaluation and mechanistic insights against epithelial cancer cells. Peptides 2016, 84, 58–67. [Google Scholar] [CrossRef]
  151. Findlay, B.; Mookherjee, N.; Schweizer, F. Ultrashort Cationic Lipopeptides and Lipopeptoids Selectively Induce Cytokine Production in Macrophages. PLoS ONE 2013, 8, e54280. [Google Scholar] [CrossRef] [PubMed]
  152. Tran, Q.G.; Ryu, A.J.; Choi, Y.J.; Jeong, K.J.; Kim, H.S.; Lee, Y.J. Enhanced production of biosurfactants through genetic engineering of Pseudozyma sp. SY16. Korean J. Chem. Eng. 2022, 39, 997–1003. [Google Scholar] [CrossRef]
Table
Table 1. Lists some microorganisms that produce surface-active compounds.
Table 1. Lists some microorganisms that produce surface-active compounds.
MicroorganismBiosurfactant/BioemulsifierReference
Acinetobacter calcoaceticus RAG-1Emulsan[57]
Acinetobacter radioresistant KA53Alasan[58]
Acinetobacter junii B6Surfactin/fengycin[59]
Acinetobacter junii BDRhamnolipids[60]
Acinetobacter calcoaceticus A2Biodispersan[61]
Bacillus nealsonii strain S2MTSurfactin[2]
Bacillus subtilis 3NASurfactin[62]
Bacillus thailandensis E264Rhamnolipids[63]
Bacillus velezensisIturin, surfactin, and fengycin[64]
Candida keroseneae GBME-IAUF-2Sophorolipids[65]
Candida lipolytica UCP 0988Rufisan[66]
Lactobacillus sp.Surfactin, iturin, and lichenysin[67]
Pseudomonas aeruginosa SGRhamnolipids[68]
Pseudomonas fluorescens SBW25Viscosine[69]
Pseudomonas sp. S2WERhamnolipids[70]
Serratia sp. ZS6 strainSerrawettina[71]
Yarrowia lipolytica IMUFRJ50682Yansan[72]
Trichosporon mycotoxinivorans CLA2Lipid-polysaccharide complex[73]
Table
Table 2. Antiviral properties of SACS.
Table 2. Antiviral properties of SACS.
Biosurfactant/
Bioemulsifier		MicroorganismAntiviral ActivityVirusReference
SurfactinBacillus subtilisRupturing the viral lipid membrane and part of the capsidSemliki Forest virus[98]
Simplex virus
(HSV-1, HSV-2)
Suid herpesvirus (SHV-1)
Inhibited the
proliferation		Simian immunodeficiency (SIV)[99]
Feline calicivirus (FCV)
Coronaviruses:
Epidemic porcine diarrhea (PEDV)
Transmissible
gastroenteritis virus (TGEV)
Lipopeptides-Inhibited the membrane fusion
between the virus and host cells. 		Influenza A (H1N1)[100]
Human Coronavirus
SARS-CoV-2		[101,102,103]
SophorolipidsCandida bombicolaVirucidal propertyHuman Immunodeficiency Virus (HIV)[104,105]
RhamnolipidsPseudomonas spp.Inhibits the
cytopathic effect		Simplex virus:[106]
HSV-1, and HSV-2;
Pseudomonas gessardii M15Inhibited the
proliferation		Simplex vírus:[12]
HSV-1 and HSV-2,
Human coronavírus:
HCoV-229E and
SARS-CoV-2
Table
Table 3. Anticancer activity of SACS against cancer cells.
Table 3. Anticancer activity of SACS against cancer cells.
Biosurfactant/
Bioemulsifier		MicroorganismAnticancer ActivityCancerReference
Rhamnolipids:
monorhamnolipid and dirhamnolipid 		P. aeruginosa MR01Inhibiting cell
division at lower concentrations		Human breast cancer MCF-7[118]
SophorolipidsWickerhamiella domercqiae Y2AIncreased the
apoptosis		HepG2 liver cancer cells[109]
CytotoxicityBreast cancer MDA-MB-231[119]
Inhibited cell
proliferation		Liver
Lung
Leukemia		[120]
Surfactin Reduced tumor growth and weight; Apoptosis; Elevated levels of immune-boosting mediatorsMelanoma skin cancer[13]
Bacillus saphensisCytotoxic activity against cancer cell linesBreast cancer
Melanoma		[46]
IturinBacillus megateriumInhibited the growth of cancer cellsBreast cancer[121]
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Araujo, J.; Monteiro, J.; Silva, D.; Alencar, A.; Silva, K.; Coelho, L.; Pacheco, W.; Silva, D.; Silva, M.; Silva, L.; et al. Surface-Active Compounds Produced by Microorganisms: Promising Molecules for the Development of Antimicrobial, Anti-Inflammatory, and Healing Agents. Antibiotics 2022, 11, 1106. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11081106

AMA Style

Araujo J, Monteiro J, Silva D, Alencar A, Silva K, Coelho L, Pacheco W, Silva D, Silva M, Silva L, et al. Surface-Active Compounds Produced by Microorganisms: Promising Molecules for the Development of Antimicrobial, Anti-Inflammatory, and Healing Agents. Antibiotics. 2022; 11(8):1106. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11081106

Chicago/Turabian Style

Araujo, Jéssica, Joveliane Monteiro, Douglas Silva, Amanda Alencar, Kariny Silva, Lara Coelho, Wallace Pacheco, Darlan Silva, Maria Silva, Luís Silva, and et al. 2022. "Surface-Active Compounds Produced by Microorganisms: Promising Molecules for the Development of Antimicrobial, Anti-Inflammatory, and Healing Agents" Antibiotics 11, no. 8: 1106. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11081106

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