Genomic Analysis of Drug-Resistant 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: 20 May 2025 | Viewed by 3070

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Department of Diagnostic and Public Health, Verona University, 37134 Verona, Italy
Interests: clinical genetics; genomics; epilepsy; genetics; biomedical science; cell biology; cell signaling; virology; bacteriology; microbiology; alternative splicing; infectious disease; sequencing; molecular virology; diagnostics
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Special Issue Information

Dear Colleagues,

With the advent of new sequencing technologies, microbiology is perfecting the approach of what, twenty years ago, was called pharmacogenomics.

The spread of antimicrobial resistance genes is considered a major public health threat. Mobile genetic elements are the drivers of spreading antimicrobial resistance by horizontal gene transfer. The study of mutations associated with resistance occurring during therapy or the presence of mobile genetic elements has made it possible to understand better the evolution of resistance. Being able to sequence the genomes of multidrug-resistant pathogens implicated in the infections allows us to understand the dynamics and the mobilization of the genes involved in the spread of antimicrobial resistance. Currently, multiple technologies allow the sequencing of a part or all of a microorganism’s genome, but they are not always used consciously.

In this Special Issue, we would like to collect papers, reviews, and case reports in which the different potentials of these sequencing technologies are highlighted in order to be able to provide the reader with an update and a broader view of the problem of drug resistance.

Dr. Erica Diani
Guest Editor

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Keywords

  • multi-drug resistant
  • mutation
  • bacteria
  • NGS
  • sequencing
  • mobile genetics elements
  • gene transfer

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Published Papers (2 papers)

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Research

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15 pages, 3672 KiB  
Article
Genomic Insight into Primary Adaptation of Mycobacterium tuberculosis to Aroylhydrazones and Nitrofuroylamides In Vitro
by Igor Mokrousov, Violina T. Angelova, Ivaylo Slavchev, Mikhail V. Bezruchko, Simeon Dimitrov, Dmitrii E. Polev, Georgi M. Dobrikov and Violeta Valcheva
Antibiotics 2025, 14(3), 225; https://doi.org/10.3390/antibiotics14030225 - 22 Feb 2025
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Abstract
Background/Objectives: New anti-tuberculosis compounds are needed to treat patients infected with multi- or extensively drug-resistant Mycobacterium tuberculosis strains. Studies based on spontaneous in vitro mutagenesis can provide insights into the possible modes of action and resistance mechanisms of such new compounds. We evaluated [...] Read more.
Background/Objectives: New anti-tuberculosis compounds are needed to treat patients infected with multi- or extensively drug-resistant Mycobacterium tuberculosis strains. Studies based on spontaneous in vitro mutagenesis can provide insights into the possible modes of action and resistance mechanisms of such new compounds. We evaluated the primary response of M. tuberculosis in vitro to the action of new aroylhydrazones and nitrofuroylamides. Methods: The reference strain H37Rv was cultured on solid media with compounds at increased concentrations relative to MIC. Resistant clones were investigated using whole-genome sequencing and bioinformatics tools to assess the role and potential impact of identified mutations. Results: Some of the mutations are significant (based on in silico analysis), located in essential genes, and therefore of particular interest. Frameshift mutations were observed in (i) Rv2702/ppgK, which is associated with starvation-induced drug tolerance and persistence in mice, and (ii) Rv3696c/glpK, which has been described as a switch on/off mutation associated with drug tolerance. Nonsynonymous substitutions were found in Rv0506/mmpS2, which belongs to the Mmp protein family involved in transport and drug efflux, and in infB, encoding the translation initiation factor IF-2. Conclusions: The primary adaptation of M. tuberculosis to the selective pressure of the tested compounds is complex and multifaceted. It involves multiple unrelated genes and pathways linked to non-specific drug tolerance, efflux systems, or mechanisms counteracting oxidative stress. Full article
(This article belongs to the Special Issue Genomic Analysis of Drug-Resistant Pathogens)
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Review

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20 pages, 352 KiB  
Review
Epidemiology and Genetic Traits of Carbapenemase-Producing Enterobacterales: A Global Threat to Human Health
by Gualtiero Alvisi, Antonio Curtoni, Rossella Fonnesu, Aurora Piazza, Caterina Signoretto, Giorgia Piccinini, Davide Sassera and Paolo Gaibani
Antibiotics 2025, 14(2), 141; https://doi.org/10.3390/antibiotics14020141 - 1 Feb 2025
Cited by 1 | Viewed by 2022
Abstract
Carbapenemase-producing Enterobacterales (CPE) represent an important threat to global health, resulting in an urgent issue in clinical settings. CPE often exhibit a multidrug-resistant (MDR) phenotype, thus reducing the antimicrobial armamentarium, with few antibiotics retaining residual antimicrobial activity against these pathogens. Carbapenemases are divided [...] Read more.
Carbapenemase-producing Enterobacterales (CPE) represent an important threat to global health, resulting in an urgent issue in clinical settings. CPE often exhibit a multidrug-resistant (MDR) phenotype, thus reducing the antimicrobial armamentarium, with few antibiotics retaining residual antimicrobial activity against these pathogens. Carbapenemases are divided into three classes (A, B, and D) according to the Ambler classification system. Among these, KPC (class A), NDM, VIM, IMP (class B), and OXA-48-like (class D) represent the most important carbapenemases in terms of diffusion and clinical impact. CPE diffusion has been observed worldwide, with current endemicity in multiple territories around the world. In this context, the clonal spread and plasmid-mediated transmission of carbapenemases have contributed to the global spread of CPE worldwide and to the diffusion of carbapenemases among different Enterobacterales species. In recent years, novel molecules showing excellent in vitro and in vivo activity have been developed against CPE. However, the recent emergence of novel traits of resistance to these molecules has already been reported in several cases, mitigating the initial promising results. This review aims to provide an updated description of the major classes of carbapenemases, their global distribution, and future perspectives to limit the diffusion of CPEs. Full article
(This article belongs to the Special Issue Genomic Analysis of Drug-Resistant Pathogens)
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