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Antibiotics
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Antibiofilm Activity against Multidrug-Resistant Pathogens
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Antibiofilm Activity against Multidrug-Resistant Pathogens

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiofilm Strategies".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 10097

Special Issue Editors

Dr. Verica Aleksic Sabo

E-Mail Website
Guest Editor
Department of Biology and Ecology, Faculty of Sciences, Trg Dositeja Obradovica 3, University of Novi Sad, 21000 Novi Sad, Serbia
Interests: multidrug-resistant bacteria; bacterial biofilm; antimicrobial agents; essential oils; phytochemicals; bacteriophages; synergistic interactions; Acinetobacter baumannii
Prof. Dr. Petar Knezevic

E-Mail Website
Guest Editor
Department of Biology and Ecology, Faculty of Sciences, Trg Dositeja Obradovica 3, University of Novi Sad, 21000 Novi Sad, Serbia
Interests: bacteriophages; antimicrobial agents; bacterial biofilm; multidrug-resistant bacteria; Pseudomonas aeruginosa; phage therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ninety-nine percent of bacteria exist in the form of a biofilm, which represents an emerging problem in global public health, causing great concern to the population, health professionals and the scientific community. Microbial biofilms possess intrinsic resistance against conventional antibiotics and cleaning procedures, with the capability to firmly adhere to surfaces for persistent contamination. The biofilm matrix provides bacteria with additional resistance power, which enables them to tolerate harsh conditions and also resist antimicrobials, which can lead to the spread of infections such as multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria. Current conventional therapies are inadequate for the safe and effective treatment of biofilms, since high doses of antibiotics are required to eradicate biofilms, indicating that biofilm treatment needs new therapeutical strategies. These global issues strongly motivate researchers to develop novel methodologies to investigate the kinetics underlying biofilm formation, to understand the response of the biofilm to different chemical and physical treatments, and to identify biofilm-specific drugs with high-throughput screenings. This Special Issue seeks manuscript submissions that improve our understanding of the process of biofilm formation in general, novel strategies for its investigation, as well as efficient agents for its treatment. Submissions on the treatment and potential eradication of biofilms using alternative antimicrobial agents (alone and in synergistic combinations) and/or novel strategies for their investigation and combined treatment to reduce their transmission and spread are especially encouraged.

Dr. Verica Aleksic Sabo
Prof. Dr. Petar Knezevic
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biofilm
  • microbial drug resistance
  • antibiofilm agents
  • antibiofilm strategies
  • synergistic interactions

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Published Papers (4 papers)

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Research

20 pages, 2736 KiB  
Article
Anti-Staphylococcus aureus Activity of Volatile Phytochemicals and Their Combinations with Conventional Antibiotics Against Methicillin-Susceptible S. aureus (MSSA) and Methicillin-Resistant S. aureus (MRSA) Strains
by Isidora Nikolic, Verica Aleksic Sabo, Damir Gavric and Petar Knezevic
Antibiotics 2024, 13(11), 1030; https://doi.org/10.3390/antibiotics13111030 - 31 Oct 2024
Viewed by 857
Abstract
Background: MSSA and MRSA strains are challenging human pathogens that can develop resistance to antibiotics, highlighting the need for alternative antimicrobial agents. Plant metabolites, particularly volatile phytochemicals, may offer promising antimicrobial properties. The aim was to evaluate the antimicrobial and antibiofilm efficacy of [...] Read more.
Background: MSSA and MRSA strains are challenging human pathogens that can develop resistance to antibiotics, highlighting the need for alternative antimicrobial agents. Plant metabolites, particularly volatile phytochemicals, may offer promising antimicrobial properties. The aim was to evaluate the antimicrobial and antibiofilm efficacy of various commercial volatile phytochemicals from the terpene and terpenoid groups against reference MSSA and MRSA strains, focusing on synergistic effects in both binary combinations and combinations with antibiotics. Methods: The microdilution method was used to determine the minimum inhibitory concentrations (MICs) for antibiotics and phytochemicals. The checkerboard method assessed synergistic interactions between phytochemicals and between phytochemicals and antibiotics, while the time-kill method was used to confirm these results. Biofilm quantification was performed using the microtiter plate method to evaluate the effects of phytochemicals, antibiotics, and their binary combinations on the eradication of 48-h-old biofilms. Results: Carvacrol and thymol demonstrated the strongest anti-staphylococcal activity, while other terpene compounds showed weaker effects. In binary combinations, carvacrol and thymol exhibited synergy against one MSSA strain (FICI = 0.50) and with tetracycline and chloramphenicol (FICI = 0.28–0.50). Synergy was also noted with streptomycin sulfate against one MRSA strain (FICI = 0.31–0.50) and with other antibiotics, including gentamicin (FICI = 0.25–0.50) and oxacillin (FICI = 0.44). Additionally, effective combinations achieved over 50% biofilm removal at both minimum inhibitory and sub-inhibitory concentrations. Conclusions: Results showed that synergy varies based on strain sensitivity to chemical agents, highlighting their potential for personalized therapy. Despite the difficulty in removing preformed biofilms, the findings highlight the importance of combined treatments to enhance antibiotic effectiveness. Full article
(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)
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17 pages, 5960 KiB  
Article
Antifungal Activity, Synergism with Fluconazole or Amphotericin B and Potential Mechanism of Direct Current against Candida albicans Biofilms and Persisters
by Peihui Zou, Jia Liu, Peng Li and Qingxian Luan
Antibiotics 2024, 13(6), 521; https://doi.org/10.3390/antibiotics13060521 - 3 Jun 2024
Cited by 1 | Viewed by 3962
Abstract
Candida albicans, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand currently available antifungals. Direct current (DC) has demonstrated a promising antimicrobial effect and synergistic effect [...] Read more.
Candida albicans, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand currently available antifungals. Direct current (DC) has demonstrated a promising antimicrobial effect and synergistic effect with antimicrobials against various infections. Here, we first found DC exerted a killing effect on C. albicans planktonic and biofilm cells. Moreover, DC showed a synergistic effect with fluconazole (FLC) and amphotericin B (AMB). Notably, near-to-complete eradication of AMB-tolerant C. albicans biofilm persisters was achieved upon DC treatment. Next, the mechanism of action of DC was explored through mapping the genes and proteomic profiles of DC-treated C. albicans. The multi-omics analysis, quantitative real-time PCR and assay of reactive oxygen species (ROS) demonstrated DC exerted an antifungal effect on C. albicans by increasing cellular oxidative stress. As revealed by multiple analyses (e.g., protein assay based on absorbance at 280 nm and rhodamine 6G assay), DC was able to enhance membrane permeability, inhibit drug efflux and increase cellular FLC/AMB concentration of C. albicans, thereby mediating its synergism with the antifungals. Furthermore, DC inhibited superoxide dismutase 2 (SOD2) expression and manganese-containing SOD (Mn SOD) activity, leading to ROS production and enhanced killing of C. albicans biofilm persisters. The current findings demonstrate that the adjunctive use of DC in combination with antifungals is a promising strategy for effective control of C. albicans infections and management of antifungal resistance/tolerance in Candida biofilms. Full article
(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)
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13 pages, 2547 KiB  
Article
Inhibition of Candida albicans Biofilm Formation and Attenuation of Its Virulence by Liriope muscari
by Jeonghoon Lee, Hyunchan Song and Kiyoung Kim
Antibiotics 2024, 13(5), 434; https://doi.org/10.3390/antibiotics13050434 - 12 May 2024
Cited by 1 | Viewed by 2114
Abstract
(1) Background: Although Candida albicans accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with Liriope muscari extract. A combination antifungal assay, [...] Read more.
(1) Background: Although Candida albicans accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with Liriope muscari extract. A combination antifungal assay, dimorphic transition assay, and adhesion assay were performed under the biofilm formation condition to determine the anti-biofilm formation effect. qRT-PCR analysis was accomplished to confirm changes in gene expression; (3) Results: L. muscari extract significantly reduces biofilm formation by 51.65% at 1.56 μg/mL use and therefore increases susceptibility to miconazole. L. muscari extract also inhibited the dimorphic transition of Candida; nearly 50% of the transition was inhibited when 1.56 μg/mL of the extract was treated. The extract of L. muscari inhibited the expression of genes related to hyphal development and extracellular matrix of 34.4% and 36.0%, respectively, as well as genes within the Ras1-cAMP-PKA, Cph2-Tec1, and MAP kinase signaling pathways of 25.58%, 7.1% and 15.8%, respectively, at 1.56 μg/mL of L. muscari extract treatment; (4) Conclusions: L. muscari extract significantly reduced Candida biofilm formation, which lead to induced antifungal susceptibility to miconazole. It suggests that L. muscari extract is a promising anti-biofilm candidate of Candida albicans since the biofilm formation of Candida albicans is an excellent target for candidiasis regulation. Full article
(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)
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16 pages, 17399 KiB  
Article
In Vitro Antibiofilm Activity of Resveratrol against Aeromonas hydrophila
by Ting Qin, Kai Chen, Bingwen Xi, Liangkun Pan, Jun Xie, Liushen Lu and Kai Liu
Antibiotics 2023, 12(4), 686; https://doi.org/10.3390/antibiotics12040686 - 31 Mar 2023
Cited by 15 | Viewed by 2467
Abstract
Aeromonas hydrophila is a Gram-negative bacterium that widely exists in various aquatic environments and causes septicemia in fish and humans. Resveratrol, a natural polyterpenoid product, has potential chemo-preventive and antibacterial properties. In this study, we investigated the effect of resveratrol on A. hydrophila [...] Read more.
Aeromonas hydrophila is a Gram-negative bacterium that widely exists in various aquatic environments and causes septicemia in fish and humans. Resveratrol, a natural polyterpenoid product, has potential chemo-preventive and antibacterial properties. In this study, we investigated the effect of resveratrol on A. hydrophila biofilm formation and motility. The results demonstrated that resveratrol, at sub-MIC levels, can significantly inhibit the biofilm formation of A. hydrophila, and the biofilm was decreased with increasing concentrations. The motility assay showed that resveratrol could diminish the swimming and swarming motility of A. hydrophila. Transcriptome analyses (RNA-seq) showed that A. hydrophila treated with 50 and 100 μg/mL resveratrol, respectively, presented 230 and 308 differentially expressed genes (DEGs), including 90 or 130 upregulated genes and 130 or 178 downregulated genes. Among them, genes related to flagellar, type IV pilus and chemotaxis were significantly repressed. In addition, mRNA of virulence factors OmpA, extracellular proteases, lipases and T6SS were dramatically suppressed. Further analysis revealed that the major DEGs involved in flagellar assembly and bacterial chemotaxis pathways could be regulated by cyclic-di-guanosine monophosphate (c-di-GMP)- and LysR-Type transcriptional regulator (LTTR)-dependent quorum sensing (QS) systems. Overall, our results indicate that resveratrol can inhibit A. hydrophila biofilm formation by disturbing motility and QS systems, and can be used as a promising candidate drug against motile Aeromonad septicemia. Full article
(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)
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