The Hidden Pandemic: Tackling Antimicrobial Resistance Mechanisms and Evolution in ESKAPE Pathogens

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: 30 June 2024 | Viewed by 6947

Special Issue Editors


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Guest Editor
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
Interests: ESKAPE pathogens, antimicrobial resistance, resistance mechanisms, pathogen evolution, bacterial pathogens, antimicrobial compounds, antibiotics, antimicrobials, mobile genetic elements, horizontal gene transfer, mutational resistance epidemiology, phylogenetics, phylogenomics, lineage replacement; virulence, biofilm, antimicrobial resistance genes, resistome molecular epidemiology; outbreak; prophage; typing genomics, transcriptomics, proteomics, infections, pathogenesis

E-Mail Website
Guest Editor
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy
Interests: multidrug-resistant gram-positive isolates; mechanisms of antibiotic resistance; Staphylococcus aureus internalization; mechanism of action of novel drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I invite you to submit papers for a Special Issue Antibiotics entitled “The Hidden Pandemic: Tackling Antimicrobial Resistance Mechanisms and Evolution in ESKAPE Pathogens”, which is dedicated to one of the most important priorities in public health. According to the WHO, the increasing antimicrobial resistance (AMR) of pathogens is a global health crisis. The lack of new antimicrobial drugs and the constant evolution of pathogens are the focal points of this challenge to public health. In this scenario, this Special Issue aims to collect studies investigating the AMR mechanisms in ESKAPE and their evolution.

This goal fits fully with Antibiotics’ aim to represent and focus in on the knowledge necessary to develop new strategies to fight and manage AMR.

Original research articles, short communications and review articles describing recent advances in the field of antimicrobial resistance mechanisms and their evolution will be considered.

Potential topics include, but are not limited to, the following:

  • Molecular mechanisms involved in bacterial resistance;
  • Omics to investigate molecular mechanisms and their evolution;
  • Response to antimicrobials or antibiotics;
  • Genetics on microorganisms to improve the effects of antimicrobials;
  • Advances in research on new/current antibiotics and antimicrobials;
  • Advances in research on alternative compounds or antimicrobial coadjuvants acting on virulence and biofilm.
  • Genetic elements involved in antimicrobial resistance;
  • Molecular Epidemiology, Phylogenomics, evolution; genomics; phylogenetic reconstruction, Lineage replacement.
  • Persistence and Tolerance.

Dr. Viviana Cafiso
Dr. Floriana Campanile
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.

Published Papers (4 papers)

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Research

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13 pages, 3416 KiB  
Article
Development of Biocompatible Ga2(HPO4)3 Nanoparticles as an Antimicrobial Agent with Improved Ga Resistance Development Profile against Pseudomonas aeruginosa
by Huda Alamri, Guanyu Chen and Songping D. Huang
Antibiotics 2023, 12(11), 1578; https://doi.org/10.3390/antibiotics12111578 - 30 Oct 2023
Viewed by 915
Abstract
Ga(III) can mimic Fe(III) in the biological system due to its similarities in charge and ionic radius to those of Fe(III) and can exhibit antimicrobial activity by disrupting the acquisition and metabolism of Fe in bacterial cells. For example, Ga(NO3)3 [...] Read more.
Ga(III) can mimic Fe(III) in the biological system due to its similarities in charge and ionic radius to those of Fe(III) and can exhibit antimicrobial activity by disrupting the acquisition and metabolism of Fe in bacterial cells. For example, Ga(NO3)3 has been proven to be effective in treating chronic lung infections by Pseudomonas aeruginosa (P. aeruginosa) in cystic fibrosis patients in a recent phase II clinical trial. However, Ga(NO3)3 is an ionic compound that can hydrolyze to form insoluble hydroxides at physiological pH, which not only reduces its bioavailability but also causes potential renal toxicity when it is used as a systemic drug. Although complexion with suitable chelating agents has offered a varying degree of success in alleviating the hydrolysis of Ga(III), the use of nanotechnology to deliver this metallic ion should constitute an ultimate solution to all the above-mentioned problems. Thus far, the development of Ga-based nanomaterials as metalloantibiotics is an underexploited area of research. We have developed two different synthetic routes for the preparation of biocompatible Ga2(HPO4)3 NPs and shown that both the PVP- or PEG-coated Ga2(HPO4)3 NPs exhibit potent antimicrobial activity against P. aeruginosa. More importantly, such polymer-coated NPs do not show any sign of Ga-resistant phenotype development after 30 passes, in sharp contrast to Ga(NO3)3, which can rapidly develop Ga-resistant phenotypes of P. aeruginosa, indicating the potential of using Ga2(HPO4)3 NPs a new antimicrobial agent in place of Ga(NO3)3. Full article
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16 pages, 1198 KiB  
Article
New Antimicrobial Resistance Strategies: An Adaptive Resistance Network Conferring Reduced Glycopeptide Susceptibility in VISA
by Elvira Aguglia, Eleonora Chines, Stefania Stefani and Viviana Cafiso
Antibiotics 2023, 12(4), 783; https://doi.org/10.3390/antibiotics12040783 - 19 Apr 2023
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Abstract
Background: Vancomycin-intermediate Staphylococcus aureus (VISA) emerges typically in the healthcare-associated methicillin-resistant S. aureus and more rarely in community-acquired S. aureus (CA-MRSA). VISA is a serious concern for public health due to its association with persistent infections, the failure of vancomycin treatment, and [...] Read more.
Background: Vancomycin-intermediate Staphylococcus aureus (VISA) emerges typically in the healthcare-associated methicillin-resistant S. aureus and more rarely in community-acquired S. aureus (CA-MRSA). VISA is a serious concern for public health due to its association with persistent infections, the failure of vancomycin treatment, and poor clinical outcomes. Currently, the burden of VISA is somewhat high, even though vancomycin is the mainstay treatment for severe MRSA infections. The molecular mechanisms of reduced glycopeptide susceptibility in S. aureus are constantly under investigation but have still not yet been fully characterized. Methods: Our goal was to investigate the reduced glycopeptide susceptibility mechanisms emerging in a VISA CA-MRSA versus its vancomycin-susceptible (VSSA) CA-MRSA parents in a hospitalized patient undergoing glycopeptide treatment. Comparative integrated omics, Illumina MiSeq whole-genome sequencing (WGS), RNA-Seq, and bioinformatics were performed. Results: Through a comparison of VISA CA-MRSA vs. its VSSA CA-MRSA parent, mutational and transcriptomic adaptations were found in a pool of genes involved, directly or indirectly, in the biosynthesis of the glycopeptide target conferring or supporting the VISA phenotype, and its cross-resistance with daptomycin. This pool included key genes responsible for the biosynthesis of the peptidoglycan precursors, i.e., D-Ala, the D-Ala-D-Ala dipeptide termini of the pentapeptide, and its incorporation in the nascent pentapeptide, as key targets of the glycopeptide resistance. Furthermore, accessory glycopeptide-target genes involved in the pathways corroborated the key adaptations, and thus, supported the acquisition of the VISA phenotype i.e., transporters, nucleotide metabolism genes, and transcriptional regulators. Finally, transcriptional changes were also found in computationally predicted cis-acting small antisense RNA triggering genes related both to the key or accessory adaptive pathways. Conclusion: Our investigation describes an adaptive resistance pathway acquired under antimicrobial therapy conferring reduced glycopeptide susceptibility in a VISA CA-MRSA due to a comprehensive network of mutational and transcriptional adaptations in genes involved in pathways responsible for the biosynthesis of glycopeptide’s target or supporters of the key resistance path. Full article
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17 pages, 814 KiB  
Article
Balancing the Virulence and Antimicrobial Resistance in VISA DAP-R CA-MRSA Superbug
by Rossella Salemi, Alessandra Zega, Elvira Aguglia, Flavia Lo Verde, Giuseppe Pigola, Stefania Stefani and Viviana Cafiso
Antibiotics 2022, 11(9), 1159; https://doi.org/10.3390/antibiotics11091159 - 27 Aug 2022
Cited by 3 | Viewed by 1759
Abstract
Background: Methicillin-resistant Staphylococcus aureus (MRSA) with intermediate resistance to Vancomycin (VISA) is reported worldwide. These strains frequently emerge among hospital-associated (HA)-MRSA and rarely within community-acquired (CA)-MRSA. Here, the genomic and transcriptomic adaptations distinguishing VISA daptomycin resistant (DAP-R) CA-MRSA, which emerged in a hospitalized [...] Read more.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) with intermediate resistance to Vancomycin (VISA) is reported worldwide. These strains frequently emerge among hospital-associated (HA)-MRSA and rarely within community-acquired (CA)-MRSA. Here, the genomic and transcriptomic adaptations distinguishing VISA daptomycin resistant (DAP-R) CA-MRSA, which emerged in a hospitalized patient under glycopeptide treatment, were explored. Methods: Whole-genome sequencing, RNA-Seq and bioinformatics were carried out. Results: Our CA-MRSA clustered in the USA400 lineage showing additional antimicrobial resistance (AMR) versus DAP and glycopeptides. Resistomics revealed adaptations related to glycopeptide, daptomycin and rifampin resistance (mprF nsSNPS and overexpression of glycopeptide and daptomycin-resistance related genes). Similar changes were detected in virulence traits (agrA HI-nsSNPs and toxin gene underexpression), in which a decrease was observed despite the abundance of virulence-related genes. Our results predicted a balance in adaptations, decreasing the virulence and biological costs to support the co-occurrence of extensive AMR in a hypervirulent genomic background. Conclusion: Our data show that VISA DAP-R CA-MRSA shifts the potential hypervirulent behavior of CA-MRSA towards the acquisition and maintenance of extensive AMR, by a decrease in virulence and biological costs mediated by a “compensatory modulatory mutation” silencing the Agr quorum-sensing cascade. Full article
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Review

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24 pages, 1569 KiB  
Review
Laboratory Evolution of Antimicrobial Resistance in Bacteria to Develop Rational Treatment Strategies
by Tomoya Maeda and Chikara Furusawa
Antibiotics 2024, 13(1), 94; https://doi.org/10.3390/antibiotics13010094 - 18 Jan 2024
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Abstract
Laboratory evolution studies, particularly with Escherichia coli, have yielded invaluable insights into the mechanisms of antimicrobial resistance (AMR). Recent investigations have illuminated that, with repetitive antibiotic exposures, bacterial populations will adapt and eventually become tolerant and resistant to the drugs. Through intensive [...] Read more.
Laboratory evolution studies, particularly with Escherichia coli, have yielded invaluable insights into the mechanisms of antimicrobial resistance (AMR). Recent investigations have illuminated that, with repetitive antibiotic exposures, bacterial populations will adapt and eventually become tolerant and resistant to the drugs. Through intensive analyses, these inquiries have unveiled instances of convergent evolution across diverse antibiotics, the pleiotropic effects of resistance mutations, and the role played by loss-of-function mutations in the evolutionary landscape. Moreover, a quantitative analysis of multidrug combinations has shed light on collateral sensitivity, revealing specific drug combinations capable of suppressing the acquisition of resistance. This review article introduces the methodologies employed in the laboratory evolution of AMR in bacteria and presents recent discoveries concerning AMR mechanisms derived from laboratory evolution. Additionally, the review outlines the application of laboratory evolution in endeavors to formulate rational treatment strategies. Full article
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