Recent Advances in the Prevention and Eradication Strategies for Combating Biofilm-Related Infections

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 20 June 2024 | Viewed by 12252

Special Issue Editors


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Guest Editor
Department of Biomedical, Surgical and Dental Sciences-One Health Unit, School of Medicine, University of Milan, Via Pascal 36, 20133 Milan, Italy
Interests: proteomics of host-pathogen interaction; immunoproteomics; metaproteomics; metagenomics; zoonotic and infectious diseases; bacterial competition
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Biomedical, Surgical and Dental Sciences - One Health Unit, University of Milan, 20133 Milan, Italy
Interests: antibiotic resistance; one health; bacterial infections; alternative to antibiotics; laboratory animals; infectious diseases
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Biomedical, Surgical and Dental Sciences-One Health Unit, School of Medicine, University of Milan, Via Pascal 36, 20133 Milan, Italy
Interests: antibiotic resistance; alternative to antibiotics; biofilm formation; nanoparticles; essential oils; whole genome sequencing; metagenomics

Special Issue Information

Dear Colleagues,

Microorganisms that can form biofilms are associated with several chronic infections, including those caused by medical devices (e.g., catheters and implants), respiratory, urinary, and wound infections, as well as chronic sinusitis, cystic fibrosis, and periodontal diseases. New strategies for combating biofilms have been developed over the years. One possible strategy is to destroy the biofilm matrix using enzymes, chelators, or nanoparticles. Bacteriophage therapy, which uses viruses to target and destroy specific bacteria within biofilms, is a fast-growing area. Combining standard antibiotics with biofilm-targeting compounds or using novel drug-delivery methods has demonstrated the potential to improve treatments’ effectiveness. This Special Issue focuses on various ways for preventing biofilm formation or controlling its development. Original research articles, short communications, reviews, and case studies are all invited. Potential topics for this Special Issue include different antibiofilm strategies, but are not limited to:

  • The phage of phage-derived enzymes;
  • The development of anti-quorum sensing molecules;
  • The use of natural products;
  • The combination of antimicrobial agents and nanoparticles with synergistic effect;
  • The description of novel surface modification techniques.

Dr. Alessio Soggiu
Dr. Piera Anna Martino
Dr. Gabriele Meroni
Guest Editors

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Keywords

  • antibiotic resistance
  • antibiofilm molecules
  • biofilm-related infections
  • biofilm-targeted therapies
  • quorum-sensing inhibitors
  • nanotechnology-based therapies
  • nanoparticles
  • enzyme-based therapies
  • bacteriophage cocktail
  • novel treatment
  • molecular target
  • natural products

Published Papers (13 papers)

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Research

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11 pages, 1806 KiB  
Article
Amount of Dentifrice and Fluoride Concentration Affect the pH and Inorganic Composition of Dual-Species Biofilms of Streptococcus mutans and Candida albicans
by Caio Sampaio, Alberto Carlos Botazzo Delbem, Thayse Yumi Hosida, Ana Vitória Pereira Fernandes, Bruna do Amaral, Leonardo Antônio de Morais, Douglas Roberto Monteiro and Juliano Pelim Pessan
Pharmaceutics 2024, 16(4), 562; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16040562 - 20 Apr 2024
Viewed by 464
Abstract
This work assessed the influence of the amount of dentifrice and fluoride (F) concentration in the product on the pH and inorganic components of Streptococcus mutans and Candida albicans dual-species biofilms. The biofilms were treated with suspensions of fluoride dentifrices containing 550 or [...] Read more.
This work assessed the influence of the amount of dentifrice and fluoride (F) concentration in the product on the pH and inorganic components of Streptococcus mutans and Candida albicans dual-species biofilms. The biofilms were treated with suspensions of fluoride dentifrices containing 550 or 1100 ppm of F (550 F or 1100 F, respectively) administered at comparable intensities: (i-1) 550 F/0.08 g or 1100 F/0.04 g; (i-2) 550 F/0.16 g or 1100 F/0.08 g; and (i-3) 550 F/0.32 g or 1100 F/0.16 g. A placebo dentifrice (without NaF, 0.32 g) was used as a negative control. After the last treatment, the biofilm pH was measured and the F, calcium (Ca), and phosphorus (P) concentrations were determined. Data were subjected to an ANOVA/Kruskal–Wallis test, and a Student–Newman–Keuls test. The highest biofilm pH and F concentrations (biomass and fluid) were observed for 1100 F at i-3. Overall, 1100 F resulted in F levels similar to 550 F for i-1 and i-2. In addition, 550 F applied at i-2 and i-3 led to higher F in the biomass/fluid compared to 1100 F applied at i-1 and i-2, respectively. In biomass, the lowest Ca concentrations were observed for 1100 F at i-3. The conclusion drawn is that the treatment intensity holds greater significance as a parameter compared to the concentration of F or the amount of dentifrice when considered individually. Full article
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23 pages, 3201 KiB  
Article
Anti-Helicobacter pylori Biofilm Extracts from Rubus idaeus and Rubus occidentalis
by Rafał Hałasa, Katarzyna Turecka, Urszula Mizerska and Mirosława Krauze-Baranowska
Pharmaceutics 2024, 16(4), 501; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16040501 - 05 Apr 2024
Viewed by 459
Abstract
Helicobacter pylori infections are still an important health problem and are directly related to the development of gastric ulcer, gastric adenocarcinoma, mucosal lymphoid tissue lymphoma, and diabetes. At the same time, the number of substances/drugs effective against these bacteria is limited due to [...] Read more.
Helicobacter pylori infections are still an important health problem and are directly related to the development of gastric ulcer, gastric adenocarcinoma, mucosal lymphoid tissue lymphoma, and diabetes. At the same time, the number of substances/drugs effective against these bacteria is limited due to increasing resistance. Raw plant materials from various species of the Rubus genus—fruits and shoots—have shown antimicrobial activity in numerous studies against different bacteria, including H. pylori in a planktonic form. Research carried out on a model using fragments of intravenous infusions and triphenyl tetrazolium chloride (TTC) as a dye showed that the shoot extract of Rubus idaeus ‘Willamette’, the fruit extract of R. idaeus ‘Poranna Rosa’, R. idaeus and R. idaeus ‘Laszka’, and R. occidentalis Litacz’ prevent the formation of biofilm by H. pylori. Active concentrations inhibiting biofilm formation were 6.65 mg/mL for shoots and 16.65 mg/mL for fruits. However, in the resulting biofilm, the extract from the shoots of R. idaeus ‘Willamette’ and the fruit of R. idaeus ‘Poranna Rosa’ at a concentration of 16.65 mg/mL was active against living bacteria, and the remaining extracts showed such activity at a concentration of 33.3 mg/mL. In studies on the interaction of the extract with antibiotics on biofilm, the extract from the shoots of R. idaeus ‘Willamette’ showed synergy with doxycycline and levofloxacin, additivity with amoxicillin and clarithromycin, and neutrality with metronidazole. H. pylori biofilm research was carried out in a newly elaborated research model—culture on fragments of intravenous infusions with the addition of TTC as a marker of living bacterial cells. The research results may constitute the basis for the development of new combination therapies for the treatment of H. pylori infections, including its resistant strains. The proposed new biofilm research model, which is cheap and effective, may allow testing of new substances that are potentially more effective against H. pylori and other biofilm-forming bacterial strains. Full article
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13 pages, 4088 KiB  
Article
Antimicrobial Effects of Some Natural Products on Adhesion and Biofilm Inhibition of Clostridioides difficile
by Dorota Wultańska, Michał Piotrowski and Hanna Pituch
Pharmaceutics 2024, 16(4), 478; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16040478 - 30 Mar 2024
Viewed by 665
Abstract
Understanding the potential antimicrobial properties of natural compounds and their impacts on Clostridioides difficile virulence factors may aid in developing alternative strategies for preventing and treating C. difficile infections (CDI). In this study, we investigated the bactericidal effects of ginger oil (GO), peppermint [...] Read more.
Understanding the potential antimicrobial properties of natural compounds and their impacts on Clostridioides difficile virulence factors may aid in developing alternative strategies for preventing and treating C. difficile infections (CDI). In this study, we investigated the bactericidal effects of ginger oil (GO), peppermint oil (PO), curcumin (CU), cinnamon aldehyde (CI), and trans-cinnamaldehyde (TCI) on the adhesion and biofilm disruption of C. difficile. We used three reference and five clinical C. difficile strains of different ribotypes. The bactericidal activity was assessed using the broth microdilution method. The adhesion was evaluated using human epithelial cell lines, and biofilm formation was visualized by confocal laser scanning microscopy. All tested strains exhibited susceptibility to CU, with minimum inhibitory concentration (MIC) values ranging from 128 µg/mL to 2048 µg/mL. Similarly, all strains were susceptible to CI and TCI, with MIC values ranging from 6.25% (v/v) to 25% (v/v). Most of the tested substances reduced the adhesion of C. difficile strains, while two tested strains showed significantly higher adhesion when co-incubated with the tested substances. Similar observations were made for biofilm formation, with observed density and morphology varied depending on the strain. In conclusion, the tested products demonstrated bactericidal activity and reduced the adhesion of C. difficile strains. They may be considered for further studies as potential antimicrobial agents targeting biofilm-related infections. Full article
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16 pages, 3062 KiB  
Article
Anti-Cariogenic Effects of S. cerevisiae and S. boulardii in S. mutans–C. albicans Cross-Kingdom In Vitro Models
by Dina Yousif, Yan Wu, Alexandria Azul Gonzales, Christa Mathieu, Yan Zeng, Lee Sample, Sabrina Terando, Ting Li and Jin Xiao
Pharmaceutics 2024, 16(2), 215; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16020215 - 01 Feb 2024
Viewed by 812
Abstract
Despite the well-documented health benefits of the probiotic Saccharomyces, its application in oral health has not been comprehensively assessed. Dental caries is a transmissible disease initiated by acid production of cariogenic bacteria and yeast, such as Streptococcus mutans and Candida albicans, [...] Read more.
Despite the well-documented health benefits of the probiotic Saccharomyces, its application in oral health has not been comprehensively assessed. Dental caries is a transmissible disease initiated by acid production of cariogenic bacteria and yeast, such as Streptococcus mutans and Candida albicans, on tooth enamel and followed by subsequent enamel demineralization. Here, we investigated the effect of two Saccharomyces strains (Saccharomyces boulardii and Saccharomyces cerevisiae) on S. mutansC. albicans cross-kingdom interactions using a cariogenic planktonic model. Viable cells, pH changes, and gene expression were measured. S. cerevisiae and S. boulardii inhibited the growth of C. albicans in dual- and multi-species conditions at 4, 6, and 20 h. Saccharomyces also inhibited C. albicans hyphal formation. Furthermore, Saccharomyces reduced the acidity of the culture medium, which usually plummeted below pH 5 when S. mutans and C. albicans were present in the model. The presence of Saccharomyces maintained the culture medium above 6 even after overnight incubation, demonstrating a protective potential against dental enamel demineralization. S. boulardii significantly down-regulated S. mutans atpD and eno gene expression. Overall, our results shed light on a new promising candidate, Saccharomyces, for dental caries prevention due to its potential to create a less cariogenic environment marked by a neutral pH and reduced growth of C. albicans. Full article
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14 pages, 4515 KiB  
Article
LC-AMP-F1 Derived from the Venom of the Wolf Spider Lycosa coelestis, Exhibits Antimicrobial and Antibiofilm Activities
by Yuxin Song, Junyao Wang, Xi Liu, Shengwei Yu, Xing Tang and Huaxin Tan
Pharmaceutics 2024, 16(1), 129; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16010129 - 19 Jan 2024
Cited by 1 | Viewed by 890
Abstract
In recent years, there has been a growing interest in antimicrobial peptides as innovative antimicrobial agents for combating drug-resistant bacterial infections, particularly in the fields of biofilm control and eradication. In the present study, a novel cationic antimicrobial peptide, named LC-AMP-F1, was derived [...] Read more.
In recent years, there has been a growing interest in antimicrobial peptides as innovative antimicrobial agents for combating drug-resistant bacterial infections, particularly in the fields of biofilm control and eradication. In the present study, a novel cationic antimicrobial peptide, named LC-AMP-F1, was derived from the cDNA library of the Lycosa coelestis venom gland. The sequence, physicochemical properties and secondary structure of LC-AMP-F1 were predicted and studied. LC-AMP-F1 was tested for stability, cytotoxicity, drug resistance, antibacterial activity, and antibiofilm activity in vitro compared with melittin, a well-studied antimicrobial peptide. The findings indicated that LC-AMP-F1 exhibited inhibitory effects on the growth of various bacteria, including five strains of multidrug-resistant bacteria commonly found in clinical settings. Additionally, LC-AMP-F1 demonstrated effective inhibition of biofilm formation and disruption of mature biofilms. Furthermore, LC-AMP-F1 exhibited favorable stability, minimal hemolytic activity, and low toxicity towards different types of eukaryotic cells. Also, it was found that the combination of LC-AMP-F1 with conventional antibiotics exhibited either synergistic or additive therapeutic benefits. Concerning the antibacterial mechanism, scanning electron microscopy and SYTOX Green staining results showed that LC-AMP-F1 increased cell membrane permeability and swiftly disrupted bacterial cell membranes to exert its antibacterial effects. In summary, the findings and studies facilitated the development and clinical application of novel antimicrobial agents. Full article
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18 pages, 5963 KiB  
Article
Lactobacillus johnsonii LJO02 (DSM 33828) Cell-Free Supernatant and Vitamin D Improve Wound Healing and Reduce Interleukin-6 Production in Staphylococcus aureus-Infected Human Keratinocytes
by Paola Zanetta, Chiara Ballacchino, Diletta Francesca Squarzanti, Angela Amoruso, Marco Pane and Barbara Azzimonti
Pharmaceutics 2024, 16(1), 18; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16010018 - 21 Dec 2023
Viewed by 1217
Abstract
Methicillin-resistant biofilm-forming Staphylococcus spp. are found in about 25% of the overall cases of chronic wounds, which can undergo malignant degeneration and be associated with skin cancer. Although antimicrobial agents are clinically used to counteract pathogens and promote wound healing, they are increasingly [...] Read more.
Methicillin-resistant biofilm-forming Staphylococcus spp. are found in about 25% of the overall cases of chronic wounds, which can undergo malignant degeneration and be associated with skin cancer. Although antimicrobial agents are clinically used to counteract pathogens and promote wound healing, they are increasingly ineffective against multi-drug resistant bacteria. Moreover, they can induce dysbiosis, which favors opportunistic pathogen infections and alters immune responses. Consequently, research on pathogen containment strategies is crucial. We aimed to evaluate the potential beneficial effect of Lactobacillus johnsonii LJO02 cell-free supernatant (CFS) and vitamin D, as single treatments or in combination, on cell viability, wound healing, and the pro-inflammatory interleukin-6 (IL-6) production of a Staphylococcus aureus-infected human immortalized keratinocyte cell line (HaCaT) in vitro model. The analysis showed that LJO02 CFS 20% v/v ratio and 100 nM vitamin D promoted infected cell viability and wound healing and significantly reduced IL-6 production. However, their effect was not synergic, since no significant difference between the single and combined treatments was observed. LJO02 CFS topic application and vitamin D supplementation could provide a valuable strategy for attenuating S. aureus-induced pathogenesis, promoting wound healing and opening new therapeutic strategies supporting the conventional approaches. Full article
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12 pages, 2147 KiB  
Article
Shock Wave-Activated Silver-Loaded Biopolymer Implant Coating Eliminates Staphylococcus epidermidis on the Surface and in the Surrounding of Implants
by Martin Schulze, Melanie Nonhoff, Julian Hasselmann, Manfred Fobker, Silke Niemann, Christoph Theil, Georg Gosheger and Jan Puetzler
Pharmaceutics 2023, 15(12), 2670; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15122670 - 25 Nov 2023
Cited by 1 | Viewed by 738
Abstract
Bacterial biofilms on foreign surfaces are considered a primary cause of implant-related infections, which are challenging to treat. A new implant coating was developed, containing anti-infective silver within a biocompatible polymer carrier substance. In addition to its passive effect on the implant surface, [...] Read more.
Bacterial biofilms on foreign surfaces are considered a primary cause of implant-related infections, which are challenging to treat. A new implant coating was developed, containing anti-infective silver within a biocompatible polymer carrier substance. In addition to its passive effect on the implant surface, highly concentrated anti-infective silver can be released as needed via the application of high-energy shock waves. This intervention could be applied transcutaneously in a clinical setting without the need for additional surgery. We investigated the inhibition of biofilm formation and the effectiveness of eradication after activation of the coating via shock waves in an in vitro biofilm model using Staphylococcus epidermidis RP62A. This was performed via scanning electron microscopy and quantitative microbiology. Additionally, we examined the cytotoxicity of the new coating on normal human fibroblasts and Saos-2 osteoblast-like cells, depending on the silver concentration. All studies were compared to uncoated titanium surfaces Ti6Al4V and a conventional electroplated silver coating. Cytotoxicity toward normal human fibroblasts and Saos-2 osteoblast-like cells increased with higher silver content but remained tolerable at 6%. Compared to uncoated Ti6Al4V and the electroplated silver coating, the new coating with a silver content of 4% and 6% exhibited a significant reduction in adherent bacteria by a factor of approximately 1000. This was also evident via microscopic examination of the surface morphology of the biofilms. Furthermore, following shock wave activation, no bacteria were detectable on either the implant or in the surrounding fluid after a 24 h period. Full article
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13 pages, 750 KiB  
Article
The Synthesis and Antibacterial Properties of Pillar[5]arene with Streptocide Fragments
by Evgenia Subakaeva, Pavel Zelenikhin, Evgenia Sokolova, Arina Pergat, Yulia Aleksandrova, Dmitriy Shurpik and Ivan Stoikov
Pharmaceutics 2023, 15(12), 2660; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15122660 - 23 Nov 2023
Viewed by 872
Abstract
The growing problem of bacterial resistance to antimicrobials actualizes the development of new approaches to solve this challenge. Supramolecular chemistry tools can overcome the limited bacterial resistance and side effects of classical sulfonamides that hinder their use in therapy. Here, we synthesized a [...] Read more.
The growing problem of bacterial resistance to antimicrobials actualizes the development of new approaches to solve this challenge. Supramolecular chemistry tools can overcome the limited bacterial resistance and side effects of classical sulfonamides that hinder their use in therapy. Here, we synthesized a number of pillar[5]arenes functionalized with different substituents, determined their ability to self-association using DLS, and characterized antimicrobial properties against S. typhimurium, K. pneumoniae, P. aeruginosa, S. epidermidis, S. aureus via a resazurin test. Biofilm prevention concentration was calculated for an agent with established antimicrobial activity by the crystal–violet staining method. We evaluated the mutagenicity of the macrocycle using the Ames test and its ability to affect the viability of A549 and LEK cells in the MTT-test. It was shown that macrocycle functionalized with sulfonamide residues exhibited antimicrobial activity an order higher than pure streptocide and also revealed the ability to prevent biofilm formation of S. aureus and P. aeruginosa. The compound did not show mutagenic activity and exhibited low toxicity to eukaryotic cells. The obtained results allow considering modification of the macrocyclic platforms with classic antimicrobials as an opportunity to give them a “second life” and return to practice with improved properties. Full article
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16 pages, 3766 KiB  
Article
Resensitisation of Methicillin-Resistant Staphylococcus aureus to Conventional Antibiotics in the Presence of an Engineered Enzybiotic
by Salim Manoharadas, Basel F. Al-Rayes, Mohammed Abdulaziz M. Almuzaini and Yasser Muteq Almohammadi
Pharmaceutics 2023, 15(10), 2511; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15102511 - 23 Oct 2023
Viewed by 746
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most dreadful pathogens relevant in community and nosocomial-related infections around the world. Resensitising MRSA to antibiotics, once it became resistant, was a tough choice due to the high adaptability of this bacteria to savage conditions. [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most dreadful pathogens relevant in community and nosocomial-related infections around the world. Resensitising MRSA to antibiotics, once it became resistant, was a tough choice due to the high adaptability of this bacteria to savage conditions. This study aimed to create a chimeric enzybiotic against MRSA and test its efficiency, either individually or in combination with antibiotics. The novel enzybiotic BAC100 was constructed by fusing the catalytic domain from the bacteriocin BacL1 from Enterococcus faecalis with the cell-wall-binding domain from protein P17 of Staphylococcus aureus bacteriophage ϕ44AHJD. Apart from its partial lone activity, BAC100 was found to resensitise the MRSA strain to traditional antibiotics, including ampicillin and tetracycline. Both drugs were able to reduce live MRSA cells by 85 and 90%, respectively, within 60 min of treatment together with BAC100. However, no significant activity was observed against MRSA when these drugs were tested independently, pointing to the inherent resistance of MRSA against these conventional antibiotics. To our knowledge, this is one of the first instances where an engineered enzybiotic was found to resensitise MRSA to conventional antibiotics. This study will pave the way for the development of similar peptides that can be used together with antibiotics against gruesome pathogens of clinical importance. Full article
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29 pages, 3192 KiB  
Article
Contribution to the Synthesis, Characterization, Separation and Quantification of New N-Acyl Thiourea Derivatives with Antimicrobial and Antioxidant Potential
by Roxana Roman, Lucia Pintilie, Diana Camelia Nuță, Miron Teodor Căproiu, Florea Dumitrașcu, Irina Zarafu, Petre Ioniță, Ioana Cristina Marinaș, Luminița Măruțescu, Eleonora Kapronczai, Simona Ardelean and Carmen Limban
Pharmaceutics 2023, 15(10), 2501; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15102501 - 20 Oct 2023
Viewed by 947
Abstract
The present study aimed to synthesize, characterize, and validate a separation and quantification method of new N-acyl thiourea derivatives (1a1o), incorporating thiazole or pyridine nucleus in the same molecule and showing antimicrobial potential previously predicted in silico. The [...] Read more.
The present study aimed to synthesize, characterize, and validate a separation and quantification method of new N-acyl thiourea derivatives (1a1o), incorporating thiazole or pyridine nucleus in the same molecule and showing antimicrobial potential previously predicted in silico. The compounds have been physiochemically characterized by their melting points, IR, NMR and MS spectra. Among the tested compounds, 1a, 1g, 1h, and 1o were the most active against planktonic Staphylococcus aureus and Pseudomonas aeruginosa, as revealed by the minimal inhibitory concentration values, while 1e exhibited the best anti-biofilm activity against Escherichia coli (showing the lowest value of minimal inhibitory concentration of biofilm development). The total antioxidant activity (TAC) assessed by the DPPH method, evidenced the highest values for the compound 1i, followed by 1a. A routine quality control method for the separation of highly related compounds bearing a chlorine atom on the molecular backbone (1g, 1h, 1i, 1j, 1m, 1n) has been developed and validated by reversed-phase high-performance liquid chromatography (RP—HPLC), the results being satisfactory for all validation parameters recommended by the ICH guidelines (i.e., system suitability, specificity, the limits of detection and quantification, linearity, precision, accuracy and robustness) and recommending it for routine separation of these highly similar compounds. Full article
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12 pages, 784 KiB  
Article
Analysis of Pathogens of Urinary Tract Infections Associated with Indwelling Double-J Stents and Their Susceptibility to Globularia alypum
by Khaireddine Bouassida, Manel Marzouk, Sahar Nouir, Rim Ghammem, Wissal Sahtout, Meriam Ghardallou, Neila Fathallah, Jalel Boukadida, Mehdi Jaidane, Raoudha Slim and Amira Zaïri
Pharmaceutics 2023, 15(10), 2496; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15102496 - 19 Oct 2023
Viewed by 989
Abstract
Ureteral double-J stents are frequently used to prevent urinary obstruction. They can develop bacterial colonization and encrustation, which leads to persistent infections that seldom respond to antibiotic treatment. Thus, the goal of this study was to evaluate the local spectrum of bacterial pathogens [...] Read more.
Ureteral double-J stents are frequently used to prevent urinary obstruction. They can develop bacterial colonization and encrustation, which leads to persistent infections that seldom respond to antibiotic treatment. Thus, the goal of this study was to evaluate the local spectrum of bacterial pathogens and their susceptibility to natural compounds. A total of 59 double-J ureteral stents from 59 consecutive patients were examined. The samples were inoculated on agar culture mediums. Extracts of Globularia alypum L. were evaluated for their antibacterial activity with the diffusion and broth dilution methods; for antibiofilm activity, the crystal violet assay was used. The identification and the quantification of the different constituents of extracts were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Bacterial growth was found in three patients (5.1%). Enterococcus faecalis (1.7%), Acinetobacter baumanii (1.7%), and Pseudomonas putida (1.7%) strains were more commonly detected. They were resistant to several common antibiotics. All extracts presented several components, mainly nepetin-7-glucoside and trans-ferulic-acid, and they had antibacterial activity (MIC = 6.25 mg/mL and MBC = 6.25 mg/mL), and antibiofilm (59.70% at 25 mg/mL) properties, especially against Acinetobacter baumanii. The results achieved confirm the important role of this plant as a source of therapeutic activities. Full article
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Review

Jump to: Research

27 pages, 2488 KiB  
Review
An Overview of Biofilm-Associated Infections and the Role of Phytochemicals and Nanomaterials in Their Control and Prevention
by Tsvetozara Damyanova, Petya D. Dimitrova, Dayana Borisova, Tanya Topouzova-Hristova, Emi Haladjova and Tsvetelina Paunova-Krasteva
Pharmaceutics 2024, 16(2), 162; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16020162 - 24 Jan 2024
Viewed by 1351
Abstract
Biofilm formation is considered one of the primary virulence mechanisms in Gram-positive and Gram-negative pathogenic species, particularly those responsible for chronic infections and promoting bacterial survival within the host. In recent years, there has been a growing interest in discovering new compounds capable [...] Read more.
Biofilm formation is considered one of the primary virulence mechanisms in Gram-positive and Gram-negative pathogenic species, particularly those responsible for chronic infections and promoting bacterial survival within the host. In recent years, there has been a growing interest in discovering new compounds capable of inhibiting biofilm formation. This is considered a promising antivirulence strategy that could potentially overcome antibiotic resistance issues. Effective antibiofilm agents should possess distinctive properties. They should be structurally unique, enable easy entry into cells, influence quorum sensing signaling, and synergize with other antibacterial agents. Many of these properties are found in both natural systems that are isolated from plants and in synthetic systems like nanoparticles and nanocomposites. In this review, we discuss the clinical nature of biofilm-associated infections and some of the mechanisms associated with their antibiotic tolerance. We focus on the advantages and efficacy of various natural and synthetic compounds as a new therapeutic approach to control bacterial biofilms and address multidrug resistance in bacteria. Full article
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34 pages, 5049 KiB  
Review
Shifting from Ammonium to Phosphonium Salts: A Promising Strategy to Develop Next-Generation Weapons against Biofilms
by Silvana Alfei
Pharmaceutics 2024, 16(1), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16010080 - 05 Jan 2024
Cited by 2 | Viewed by 1060
Abstract
Since they are difficult and sometimes impossible to treat, infections sustained by multidrug-resistant (MDR) pathogens, emerging especially in nosocomial environments, are an increasing global public health concern, translating into high mortality and healthcare costs. In addition to having acquired intrinsic abilities to resist [...] Read more.
Since they are difficult and sometimes impossible to treat, infections sustained by multidrug-resistant (MDR) pathogens, emerging especially in nosocomial environments, are an increasing global public health concern, translating into high mortality and healthcare costs. In addition to having acquired intrinsic abilities to resist available antibiotic treatments, MDR bacteria can transmit genetic material encoding for resistance to non-mutated bacteria, thus strongly decreasing the number of available effective antibiotics. Moreover, several pathogens develop resistance by forming biofilms (BFs), a safe and antibiotic-resistant home for microorganisms. BFs are made of well-organized bacterial communities, encased and protected in a self-produced extracellular polymeric matrix, which impedes antibiotics’ ability to reach bacteria, thus causing them to lose efficacy. By adhering to living or abiotic surfaces in healthcare settings, especially in intensive care units where immunocompromised older patients with several comorbidities are hospitalized BFs cause the onset of difficult-to-eradicate infections. In this context, recent studies have demonstrated that quaternary ammonium compounds (QACs), acting as membrane disruptors and initially with a low tendency to develop resistance, have demonstrated anti-BF potentialities. However, a paucity of innovation in this space has driven the emergence of QAC resistance. More recently, quaternary phosphonium salts (QPSs), including tri-phenyl alkyl phosphonium derivatives, achievable by easy one-step reactions and well known as intermediates of the Wittig reaction, have shown promising anti-BF effects in vitro. Here, after an overview of pathogen resistance, BFs, and QACs, we have reviewed the QPSs developed and assayed to this end, so far. Finally, the synthetic strategies used to prepare QPSs have also been provided and discussed to spur the synthesis of novel compounds of this class. We think that the extension of the knowledge about these materials by this review could be a successful approach to finding effective weapons for treating chronic infections and device-associated diseases sustained by BF-producing MDR bacteria. Full article
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