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Antibiofilm Efficacy of Natural and Natural-Based Products

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 33301

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Special Issue Editor

Prof. Dr. Anwar Rayan

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Guest Editor

Head of Drug Discovery Informatics Lab, Qasemi Research Center, Al-Qasemi Academic College, P.O. Box 124, Baqa El-Gharbia 30100, Israel
Interests: natural products; antibacterial activity; antidiabetic activity; anticancer activity; anti-inflammatory activity; drug discovery informatics; QSAR

Special Issue Information

Dear Colleagues,

Pathogenic microbial bioﬁlm, which is formed by microbial cells that are embedded in a self-produced polymer matrix, is considered a worldwide challenge because of its high resistance to known antimicrobial agents. In 2018, antimicrobial resistance caused 700,000 deaths worldwide, and according to a certain estimation, if the issue is not addressed properly, the number could grow to more than ten million annually by 2050. This highlights the urgent need to intensify efforts to combat antimicrobial resistance generally, and pathogenic biofilms particularly. Chemical synthesis and natural sources are two options for developing novel antimicrobial drug candidates. However, “natural products have been optimized to interact with biological systems through a long selection process, and because of this, nature is considered the best concocter of medicines and has been a source of medicines for millennia” (Kacergius T. et al, (2017). Molecular Medicine Reports. 16: 949-956). Thus, discovering novel molecules or compositions from natural sources to combat microbial biofilms is considered of high importance and could contribute to the process of filling the shortage in effective novel antimicrobial drug candidates.

During the last decade, studies on microbial biofilm have increased considerably, and we are witnessing an increase in the number of publications in peer-reviewed journals. The aim of this Special Issue is to spot recent advances in antibiofilm research of natural and natural-based products. This Special Issue may include original research articles and reviews on the efficacy of extracts, essential oils, fractions, purified compounds, and synergistic mixtures against biofilm formation from bacteria or fungi.

Prof. Anwar Rayan
Guest Editor

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Keywords

Antimicrobial
Microbial biofilm
Natural product

Published Papers (10 papers)

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Research

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20 pages, 2577 KiB

Open AccessFeature PaperArticle

Effects of Melaleuca alternifolia Chell (Tea Tree) and Eucalyptus globulus Labill. Essential Oils on Antibiotic-Resistant Bacterial Biofilms

by Ramona Iseppi, Martina Mariani, Stefania Benvenuti, Eleonora Truzzi and Patrizia Messi

Molecules 2023, 28(4), 1671; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28041671 - 09 Feb 2023

Cited by 5 | Viewed by 2302

Abstract

In the present investigation, the anti-biofilm potential of two essential oils (EOs), Melaleuca alternifolia Chell (Tea-Tree) (TTO) and Eucalyptus globulus Labill. (EEO) was characterized and tested “in vitro” against both mature biofilms and biofilms in the process of formation, produced by strains belonging to three main categories of antibiotic resistant bacteria (ARB): Vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and broad-spectrum β-lactamase-producing Escherichia coli (ESBL). The study was carried out in 96-well microtiter-plates using EOs alone, in association with each other and in combination with antibiotics against both single and multi-species biofilm. The study demonstrated the ability of TTO and EEO to counteract the ARB strains in sessile form, with promising results in particular against the biofilm in formation. Mature biofilm by ESBL E. coli was the most sensitive in the results from the quantification study of viable cells performed in multi-species biofilms. Lastly, in all tests, carried out using TTO/EEO associations and EOs/antibiotic combinations, the synergistic effect which emerged from the FIC-index has been confirmed, and both the reduction of biofilm in formation, and the removal of mature structure was obtained at very low concentrations, with values from 4 to >512-fold lower than the minimum inhibitory concentration (MIC) of the single compounds. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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18 pages, 666 KiB

Open AccessArticle

Chemical Composition, Antioxidant, and Antibiofilm Properties of Essential Oil from Thymus capitatus Plants Organically Cultured on the Greek Island of Lemnos

by Eirini Maniki, Dimitra Kostoglou, Nikolaos Paterakis, Anastasios Nikolaou, Yiannis Kourkoutas, Alexandros Papachristoforou and Efstathios Giaouris

Molecules 2023, 28(3), 1154; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28031154 - 24 Jan 2023

Cited by 2 | Viewed by 2293

Abstract

Essential oils (EOs) are mixtures of volatile plant secondary metabolites and have been exploited by humans for thousands of years for various purposes because of their many bioactivities. In this study, the EO from Thymus capitatus, a thyme species organically cultured on the Greek Island of Lemnos, was analyzed for its chemical composition (through GC-FID and GC-MS), antioxidant activity (AA), and total phenolic content (TPC), as well as its antimicrobial and antibiofilm actions against three important foodborne bacterial pathogens (Salmonella enterica ser. Typhimurium, Listeria monocytogenes, and Yersinia enterocolitica). For the latter investigations, the minimum inhibitory concentrations (MICs) and minimum biofilm inhibitory concentrations (MBICs) of the EO against the planktonic and biofilm growth of each pathogen were determined, together with the minimum biofilm eradication concentrations (MBECs). Results revealed that T. capitatus EO was rich in thymol, p-cymene, and carvacrol, presenting high AA and TPC (144.66 μmol Trolox^TM equivalents and 231.32 mg gallic acid equivalents per g of EO, respectively), while its MICs and MBICs ranged from 0.03% to 0.06% v/v and 0.03% to 0.13% v/v, respectively, depending on the target pathogen. The EO was able to fully destroy preformed (mature) biofilms of all three pathogenic species upon application for 15 min, with MBECs ranging from 2.00 to 6.25% v/v. Overall, the results demonstrate that the EO of organically cultured T. capitatus presents strong antioxidant, antibacterial, and antibiofilm properties and could, therefore, be further exploited as a functional and antimicrobial natural formulation for food and health applications. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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13 pages, 1047 KiB

Open AccessArticle

Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates

by Sobia Mastoor, Fizza Nazim, Syed Rizwan-ul-Hasan, Khalid Ahmed, Shabnam Khan, Syed Nawazish Ali and Syed Hani Abidi

Molecules 2022, 27(20), 6874; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27206874 - 13 Oct 2022

Cited by 9 | Viewed by 3666

Abstract

(1) Background: Staphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillin-resistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75–160 mg/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), α-methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15–92%) biofilm inhibition/reduction percentage capacity at the concentration of 1–10 mg/mL. Gene expression analysis showed that salicylaldehyde, α-methyl-trans-cinnamaldehyde, and α-bromo-trans-cinnamaldehyde resulted in a significant (p < 0.05) downregulation of the expression of ica-A, clf-A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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20 pages, 1689 KiB

Open AccessArticle

Screening Papaveraceae as Novel Antibiofilm Natural-Based Agents

by Sylwia Zielińska, Magdalena Dziągwa-Becker, Adam Junka, Ewelina Piątczak, Anna Jezierska-Domaradzka, Malwina Brożyna, Justyna Paleczny, Aleksandra Sobiecka, Wojciech Słupski, Eleonora Mess, Mariusz Kucharski, Serhat Sezai Çiçek, Christian Zidorn and Adam Matkowski

Molecules 2021, 26(16), 4778; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26164778 - 06 Aug 2021

Cited by 7 | Viewed by 3004

Abstract

The antimicrobial properties of herbs from Papaveraceae have been used in medicine for centuries. Nevertheless, mutual relationships between the individual bioactive substances contained in these plants remain poorly elucidated. In this work, phytochemical composition of extracts from the aerial and underground parts of five Papaveraceae species (Chelidonium majus L., Corydalis cava (L.) Schweigg. and Körte, C. cheilanthifolia Hemsl., C. pumila (Host) Rchb., and Fumaria vaillantii Loisel.) were examined using LC-ESI-MS/MS with a triple quadrupole analyzer. Large differences in the quality and quantity of all analyzed compounds were observed between species of different genera and also within one genus. Two groups of metabolites predominated in the phytochemical profiles. These were isoquinoline alkaloids and, in smaller amounts, non-phenolic carboxylic acids and phenolic compounds. In aerial and underground parts, 22 and 20 compounds were detected, respectively. These included: seven isoquinoline alkaloids: protopine, allocryptopine, coptisine, berberine, chelidonine, sanguinarine, and chelerythrine; five of their derivatives as well as non-alkaloids: malic acid, trans-aconitic acid, quinic acid, salicylic acid, trans-caffeic acid, p-coumaric acid, chlorogenic acid, quercetin, and kaempferol; and vanillin. The aerial parts were much richer in phenolic compounds regardless of the plant species. Characterized extracts were studied for their antimicrobial potential against planktonic and biofilm-producing cells of S. aureus, P. aeruginosa, and C. albicans. The impact of the extracts on cellular metabolic activity and biofilm biomass production was evaluated. Moreover, the antimicrobial activity of the extracts introduced to the polymeric carrier made of bacterial cellulose was assessed. Extracts of C. cheilanthifolia were found to be the most effective against all tested human pathogens. Multiple regression tests indicated a high antimicrobial impact of quercetin in extracts of aerial parts against planktonic cells of S. aureus, P. aeruginosa, and C. albicans, and no direct correlation between the composition of other bioactive substances and the results of antimicrobial activity were found. Conclusively, further investigations are required to identify the relations between recognized and unrecognized compounds within extracts and their biological properties. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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10 pages, 2745 KiB

Open AccessArticle

Chitosan Oligosaccharides Coupling Inhibits Bacterial Biofilm-Related Antibiotic Resistance against Florfenicol

by Xianghua Yuan, Jing Liu, Ruilian Li, Junlin Zhou, Jinhua Wei, Siming Jiao, Zhuo A. Wang and Yuguang Du

Molecules 2020, 25(24), 6043; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25246043 - 21 Dec 2020

Cited by 9 | Viewed by 2138

Abstract

The formation of bacterial biofilms has increased the resistance of bacteria to various environmental factors and is tightly associated with many persistent and chronic bacterial infections. Herein we design a strategy conjugating florfenicol, an antibiotic commonly used in the treatment of streptococcus, with the antimicrobial biomaterial, chitosan oligosaccharides. The results demonstrated that the florfenicol-COS conjugate (F-COS) efficiently eradicated the mature Streptococcus hyovaginalis biofilm, apparently inhibiting drug resistance to florfenicol. A quantity of 250 μg/mL F-COS showed effective inhibitory activity against planktonic cells and biofilm of the bacteria, and a 4-fold improvement of the F-COS compared to unmodified florfenicol was observed. Furthermore, the conjugate showed a broad-spectrum activity against both Gram-positive and Gram-negative bacteria. It suggested that F-COS might have a potential for application in the treatment of biofilm-related infections. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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14 pages, 2595 KiB

Open AccessArticle

Lauryl Gallate Activity and Streptococcus mutans: Its Effects on Biofilm Formation, Acidogenicity and Gene Expression

by Vika Gabe, Mouhammad Zeidan, Tomas Kacergius, Maksim Bratchikov, Mizied Falah and Anwar Rayan

Molecules 2020, 25(16), 3685; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25163685 - 13 Aug 2020

Cited by 10 | Viewed by 2502

Abstract

Streptococcus mutans bacterium is implicated in the pathogenesis of dental caries due to the production of biofilm and organic acids from dietary sucrose. Despite the availability of various means of prophylaxis, caries still has a high worldwide prevalence. Therefore, it is important to find new pharmaceuticals to inhibit S. mutans biofilm formation and acidogenicity. The aim of the current study was to evaluate the activity of lauryl gallate (dodecyl gallate) against S. mutans acidogenicity, the expression of biofilm-associated genes, and biofilm development on solid surfaces (polystyrene, glass). The biofilm quantities produced by S. mutans bacteria were assessed using colorimetric and optical profilometry techniques. Acidogenicity was evaluated by measuring the pH of the biofilm growth medium with microelectrode. Assessment of the expression of gene coding for glucan-binding protein B (gbpB), glucosyltranferases B, -C, -D (gtfB, -C, -D), and the F-ATPase β subunit of F₁ protein (atpD) was carried out using a quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The results demonstrate the capacity of lauryl gallate to significantly inhibit S. mutans acidogenicity and biofilm development on solid surfaces, in a dose-dependent manner, compared to untreated bacteria (p < 0.05). The highest activity of lauryl gallate occurred at a concentration of 98.98 µM, at which it suppressed biofilm formation by 100% and lowered pH levels by 98%. The effect of lauryl gallate treatment on gene expression changes, as demonstrated by our RT-qPCR data, was limited to the gtfD gene only, was a significant (48%) decrease in gene expression, obtained for the biofilm-producing bacteria, while a 300% increase in fold change for the same gene occurred in the planktonic cells. It is important to note that in previous studies we showed a broader effect of related derivatives. However, a similar magnitude of difference in effects between biofilm and planktonic cells for the atpD gene was obtained after treatment with octyl gallate and reverse magnitude for the same gene after treatment with ethyl gallate. Therefore, to ascertain the possible direct or indirect effects of lauryl gallate, as well as octyl gallate and ethyl gallate, more research is needed to examine the effects on the amount of enzymes and on the enzymatic activity of the products of the affected genes that are involved in the production and maintenance of biofilm by S. mutans. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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13 pages, 1924 KiB

Open AccessArticle

Vitamin C Enhances the Antibacterial Activity of Honey against Planktonic and Biofilm-Embedded Bacteria

by Juraj Majtan, Martin Sojka, Helena Palenikova, Marcela Bucekova and Viktor Majtan

Molecules 2020, 25(4), 992; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25040992 - 23 Feb 2020

Cited by 30 | Viewed by 7078

Abstract

Multifactorial antibacterial action is an important feature of honey; however, its bactericidal efficacy against biofilm-embedded bacteria is limited. The aim of this study was to investigate the impact of vitamin C (Vit C) on the antibacterial activity of natural honeys against planktonic as well as biofilm-embedded bacterial pathogens. The antibacterial activity of four honey samples supplemented with Vit C was expressed as the minimum inhibitory concentration (MIC). At sub-MICs, Vit C significantly increased the antibacterial activity of the tested honeys against Pseudomonas aeruginosa in planktonic cultures. However, after supplementation, honeydew honey, the most active honey, was ineffective against Staphylococcus aureus. On the other hand, when 100% honeydew honey was supplemented with Vit C (100 mg/g of honey) in a multispecies wound biofilm model, complete eradication of almost all bacterial isolates, including S. aureus, was observed. Furthermore, a mixture of honey and Vit C was partially effective against Enterococcus faecalis, whereas honey alone exhibited no antibacterial activity against this bacterium. Vit C counteracted hydrogen peroxide in honey solution and, thus, eliminated the major antibacterial compound present in honey. It is likely that a combination of honey with Vit C may trigger the intracellular production of reactive oxygen species in bacterial cells, but the exact cellular mechanisms warrant further investigations. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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17 pages, 2699 KiB

Open AccessArticle

Bio-Guided Fractionation of Prenylated Benzaldehyde Derivatives as Potent Antimicrobial and Antibiofilm from Ammi majus L. Fruits-Associated Aspergillus amstelodami

by Noha Fathallah, Marwa M. Raafat, Marwa Y. Issa, Marwa M. Abdel-Aziz, Mokhtar Bishr, Mostafa A. Abdelkawy and Osama Salama

Molecules 2019, 24(22), 4118; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24224118 - 14 Nov 2019

Cited by 35 | Viewed by 3574

Abstract

Ammi majus L.; Family Apiaceae; is a plant indigenous to Egypt. Its fruits contain bioactive compounds such as furanocoumarins and flavonoids of important biological activities. An endophytic fungus was isolated from the fruits and identified as Aspergillus amstelodami (MK215708) by morphology, microscopical characterization, and molecular identification. To our knowledge this is the first time an endophytic fungus has been isolated from the fruits. The antimicrobial activity of the Ammi majus ethanol fruits extract (AME) and fungal ethyl acetate extract (FEA) were investigated, where the FEA showed higher antimicrobial activity, against all the tested standard strains. Phytochemical investigation of the FEA extract yielded five prenylated benzaldehyde derivative compounds isolated for the first time from this species: Dihydroauroglaucin (1), tetrahydroauroglaucin (2), 2-(3,6-dihydroxyhepta-1,4-dien-1-yl)-3,6-dihydroxy-5-(dimethylallyl)benzaldehyde (3), isotetrahydroauroglaucin )4), and flavoglaucin (5). Structure elucidation was carried out using (1H- and 13C-NMR). Fractions and the major isolated compound 1 were evaluated for their antimicrobial and antibiofilm activity. Compound 1 showed high antimicrobial activity against Escherichia coli with minimum inhibitory concentration (MIC) = 1.95 µg/mL, Streptococcus mutans (MIC = 1.95 µg/mL), and Staphylococcus aureus (MIC = 3.9 µg/mL). It exhibited high antibiofilm activity with minimum biofilm inhibitory concentration (MBIC) = 7.81 µg/mL against Staphylococcus aureus and Escherichia coli biofilms and MBIC = 15.63 µg/mL against Streptococcus mutans and Candida albicans and moderate activity (MBIC = 31.25 µg/mL) against Pseudomonas aeruginosa biofilm. This reveals that dihydroauroglaucin, a prenylated benzaldehyde derivative, has a broad spectrum antimicrobial activity. In conclusion, it was observed that the MICs of the FEA are much lower than that of the AME against all susceptible strains, confirming that the antimicrobial activity of Ammi majus may be due to the ability of its endophytic fungi to produce effective secondary metabolites. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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Review

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17 pages, 802 KiB

Open AccessReview

Alkyl Gallates as Potential Antibiofilm Agents: A Review

by Mahmoud Rayan, Saleh Abu Lafi, Mizied Falah, Tomas Kacergius, Agne Kirkliauskiene, Vika Gabe and Anwar Rayan

Molecules 2023, 28(4), 1751; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28041751 - 12 Feb 2023

Cited by 3 | Viewed by 1571

Abstract

Biofilms, which consist of microorganisms embedded in a polymer-rich matrix, contribute to a variety of infections and increase antimicrobial resistance. Thus, there is a constant need to develop new chemotherapeutic agents to combat biofilms. This review article focuses on the use of alkyl gallates, gallic acid and its esters (methyl, ethyl, propyl, butyl, hexyl, octyl, and dodecyl gallate), most of which are found in plants, to inhibit biofilm formation. The studies under review reveal that alkyl gallates have the capacity to prevent biofilm development and eradicate mature biofilms through mechanisms that suppress the synthesis of the extracellular polymeric matrix, inhibit quorum-sensing signaling, and alter the microbial cell membrane. The effects are stronger the greater the length of the alkyl chain. Moreover, the alkyl gallates’ preventive activity against biofilm formation occurs at doses below the minimum inhibitory concentration. More importantly, combining alkyl gallates with antimicrobials or blue-light irradiation produces a synergistic effect on the inhibition of biofilm formation that can be used to treat infections and overcome microbial resistance. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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22 pages, 1709 KiB

Open AccessReview

Strategies and Approaches for Discovery of Small Molecule Disruptors of Biofilm Physiology

by Michael A. Trebino, Rahul D. Shingare, John B. MacMillan and Fitnat H. Yildiz

Molecules 2021, 26(15), 4582; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26154582 - 29 Jul 2021

Cited by 5 | Viewed by 3715

Abstract

Biofilms, the predominant growth mode of microorganisms, pose a significant risk to human health. The protective biofilm matrix, typically composed of exopolysaccharides, proteins, nucleic acids, and lipids, combined with biofilm-grown bacteria’s heterogenous physiology, leads to enhanced fitness and tolerance to traditional methods for treatment. There is a need to identify biofilm inhibitors using diverse approaches and targeting different stages of biofilm formation. This review discusses discovery strategies that successfully identified a wide range of inhibitors and the processes used to characterize their inhibition mechanism and further improvement. Additionally, we examine the structure–activity relationship (SAR) for some of these inhibitors to optimize inhibitor activity. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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