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Antibiotics
Special Issues
Antimicrobial Resistance Evolution and New Strategies to Fight It
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Antimicrobial Resistance Evolution and New Strategies to Fight It

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (20 December 2024) | Viewed by 9098

Special Issue Editor

Dr. Elena Perrin

E-Mail Website
Guest Editor
Department of Biology, University of Florence, Via Madonna del Piano 6, I-50019 Sesto Fiorentino, Italy
Interests: antimicrobial resistance; RND; evolution of resistance mechanisms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial resistance (AMR) remains a major public challenge and is included among the top 10 threats to global health by the World Health Organization (WHO). According to recent estimates, in 2019, 1.27 million deaths were directly attributed to drug-resistant infections globally. By 2050, up to 10 million deaths could occur annually.

This Special Issue invites articles on AMR mechanisms and their spread and evolution, but also on possible alternative strategies to the use of antibiotics, including, but not limited to, the following topics:

  • The evolution and spread of known mechanisms of AR and the emergence of new mechanisms;
  • The connections between AR, physiology, and cellular metabolism;
  • The identification of unconventional genes involved directly or indirectly in AR;
  • Possible alternative strategies to the use of antibiotics (e.g., drug repositioning, phage therapy, and anti-virulence molecules).

Dr. Elena Perrin
Guest Editor

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

  • AMR mechanisms
  • AMR spread
  • AMR evolution
  • drug repositioning
  • anti-virulence molecules
  • phage therapy

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

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Research

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17 pages, 7112 KiB  
Article
Antimicrobial and Antibiofilm Activity of Auranofin and Its Two Derivatives Bearing Naproxen and Acetylcysteine as Ligands Against Staphylococci
by Caterina Ferretti, Lorenzo Chiaverini, Noemi Poma, Andrea Dalli, Riccardo Di Leo, Laura Rindi, Alessandro Marrone, Iogann Tolbatov, Diego La Mendola, Arianna Tavanti, Tiziano Marzo and Mariagrazia Di Luca
Antibiotics 2025, 14(2), 118; https://doi.org/10.3390/antibiotics14020118 - 23 Jan 2025
Cited by 1 | Viewed by 1187
Abstract
Background/Objectives: The ability of bacteria to form biofilms makes them more tolerant to traditional antibiotics. Given the lack of new antibiotic development, drug repurposing offers a strategy for discovering new treatments. Auranofin (AF), a gold-based compound indicated for the treatment of rheumatoid [...] Read more.
Background/Objectives: The ability of bacteria to form biofilms makes them more tolerant to traditional antibiotics. Given the lack of new antibiotic development, drug repurposing offers a strategy for discovering new treatments. Auranofin (AF), a gold-based compound indicated for the treatment of rheumatoid arthritis, shows promising antibacterial activity. This study investigates the antimicrobial and antibiofilm activity of AF and its two derivatives in which the thiosugar ligand is replaced by acetylcysteine (AF-AcCys) or naproxen (AF-Napx), against Staphylococcus aureus and Staphylococcus epidermidis. Methods: AF was conjugated by transmetalation with either naproxen or acetylcysteine. Assessments of their stability in DMSO/H2O and lipophilicity expressed as the LogP were performed. The antimicrobial activity of AF and its analogues were investigated by broth microdilution assay to determine the minimum inhibitory concentration (MIC) and versus biofilm to obtain the minimum bactericidal biofilm concentration (MBBC) and minimum biofilm eradication concentration (MBEC). Results: AF derivatives were found to be stable in a DMSO/H2O mixture for 48 h. AF-Napx showed a LogP = 1.25 ± 0.22, close to AF, while AF-AcCys had a LogP = −0.95. MIC values of S. aureus and S. epidermidis were ranging from 2 µM to 0.25 µM, and ≤0.12 µM, respectively. Both AF and AF-Napx maintained efficacy against biofilm-embedded S. aureus and S. epidermidis at non-cytotoxic concentrations, with AF-Napx demonstrating lower MBBC values for S. epidermidis. Conclusions: AF, and especially its naproxen conjugate, holds potential as a therapeutic agent for treating biofilm-associated infections caused by S. aureus and S. epidermidis, particularly in device-related infections where both infection and inflammation are present. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Evolution and New Strategies to Fight It)
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12 pages, 1816 KiB  
Communication
Novel Fosfomycin Resistance Mechanism in Pseudomonas entomophila Due to Atypical Pho Regulon Control of GlpT
by Laura Sánchez-Maroto, Pablo Gella and Alejandro Couce
Antibiotics 2024, 13(11), 1008; https://doi.org/10.3390/antibiotics13111008 - 26 Oct 2024
Viewed by 1305
Abstract
Background/Objectives: Pseudomonas entomophila is a ubiquitous bacterium capable of killing insects of different orders and has become a model for host–pathogen studies and a promising tool for biological pest control. In the human pathogen Pseudomonas aeruginosa, spontaneous resistance to fosfomycin arises [...] Read more.
Background/Objectives: Pseudomonas entomophila is a ubiquitous bacterium capable of killing insects of different orders and has become a model for host–pathogen studies and a promising tool for biological pest control. In the human pathogen Pseudomonas aeruginosa, spontaneous resistance to fosfomycin arises almost exclusively from mutations in the glycerol-3-phosphate transporter (GlpT), the drug’s sole entry route in this species. Here, we investigated whether this specificity is conserved in P. entomophila, as it could provide a valuable marker system for studying mutation rates and spectra and for selection in genetic engineering. Methods: We isolated 16 independent spontaneous fosfomycin-resistant mutants in P. entomophila, and studied the genetic basis of the resistance using a combination of sequencing, phenotyping and computational approaches. Results: We only found two mutants without alterations in glpT or any of its known regulatory elements. Whole-genome sequencing revealed unique inactivating mutations in phoU, a key regulator of the phosphate starvation (Pho) regulon. Computational analyses identified a PhoB binding site in the glpT promoter, and experiments showed that phoU inactivation reduced glpT expression nearly 20-fold. While placing a sugar-phosphate transporter under the Pho regulon may seem advantageous, bioinformatic analysis shows this configuration is atypical among pseudomonads. Conclusions: This atypical Pho regulon control of GlpT probably reflects the peculiarities of P. entomophila’s habitat and lifestyle; highlighting how readily regulatory evolution can lead to the rapid divergence of resistance mechanisms, even among closely related species. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Evolution and New Strategies to Fight It)
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Review

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19 pages, 1575 KiB  
Review
The Evolution of Antimicrobial Resistance in Acinetobacter baumannii and New Strategies to Fight It
by Viola Camilla Scoffone, Gabriele Trespidi, Giulia Barbieri, Arooba Arshad, Aygun Israyilova and Silvia Buroni
Antibiotics 2025, 14(1), 85; https://doi.org/10.3390/antibiotics14010085 - 14 Jan 2025
Cited by 4 | Viewed by 3375
Abstract
Acinetobacter baumannii is considered one of the prioritized ESKAPE microorganisms for the research and development of novel treatments by the World Health Organization, especially because of its remarkable persistence and drug resistance. In this review, we describe how this can be acquired by [...] Read more.
Acinetobacter baumannii is considered one of the prioritized ESKAPE microorganisms for the research and development of novel treatments by the World Health Organization, especially because of its remarkable persistence and drug resistance. In this review, we describe how this can be acquired by the enzymatic degradation of antibiotics, target site modification, altered membrane permeability, multidrug efflux pumps, and their ability to form biofilms. Also, the evolution of drug resistance in A. baumannii, which is mainly driven by mobile genetic elements, is reported, with particular reference to plasmid-associated resistance, resistance islands, and insertion sequences. Finally, an overview of existing, new, and alternative therapies is provided. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Evolution and New Strategies to Fight It)
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13 pages, 6844 KiB  
Review
The Many Lives of Auranofin: How an Old Anti-Rheumatic Agent May Become a Promising Antimicrobial Drug
by Francesca Coscione, Stefano Zineddu, Valentina Vitali, Marco Fondi, Luigi Messori and Elena Perrin
Antibiotics 2024, 13(7), 652; https://doi.org/10.3390/antibiotics13070652 - 15 Jul 2024
Cited by 3 | Viewed by 2369
Abstract
Auranofin (AF) is a gold-based compound with a well-known pharmacological and toxicological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antiviral, antitumor, and antibacterial drug. In this [...] Read more.
Auranofin (AF) is a gold-based compound with a well-known pharmacological and toxicological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antiviral, antitumor, and antibacterial drug. In this review we focused on the antibacterial properties of AF, specifically researching the minimal inhibitory concentrations (MIC) of AF in both mono- and diderm bacteria reported so far in literature. AF proves to be highly effective against monoderm bacteria, while diderm are far less susceptible, probably due to the outer membrane barrier. We also reported the current mechanistic hypotheses concerning the antimicrobial properties of AF, although a conclusive description of its antibacterial mode of action is not yet available. Even if its mechanism of action has not been fully elucidated yet and further studies are required to optimize its delivery strategy, AF deserves additional investigation because of its unique mode of action and high efficacy against a wide range of pathogens, which could lead to potential applications in fighting antimicrobial resistance and improving therapeutic outcomes in infectious diseases. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Evolution and New Strategies to Fight It)
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