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Antibiotics
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Microbial Drug Resistance Genes
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Microbial Drug Resistance Genes

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 (31 July 2020) | Viewed by 28224

Special Issue Editor

Dr. Tim Downing

E-Mail Website
Guest Editor
Biotechnology, Dublin City University, Dublin, Ireland
Interests: genome evolution; pathogens; population genetics; hybridisation; cancer genomics

Special Issue Information

Dear Colleagues,

This Special Issue on "Microbial Drug Resistance Genes" encompasses all fields linked to pathogens' genes, genotypes and elements facilitating resistance to drugs, antibiotics and antimicrobial agents, including viral, protozoal, bacterial, fungal and algal pathogens. Particular consideration will be given to transdisciplinary research synthesizing molecular, cellular, microbiological, computational and epidemiological approaches to pathogen drug resistance. Studies assessing interactions among multi- and pan-drug resistance phenotypes and their genetic basis are encouraged, along with those examining the genomic and evolutionary context of mobilized, amplified or rearranged drug resistance genes. Lastly, papers bridging molecular diagnostics and surveillance of genetic elements associated with drug resistance would be appreciated.

Dr. Tim Downing
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

  • Pathogen
  • AMR
  • genome
  • mechanism
  • outbreak
  • phylogenetics
  • evolution
  • infection
  • virulence
  • drug
  • gene

Published Papers (6 papers)

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Research

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16 pages, 4433 KiB  
Article
The Cell Envelope Stress Response of Bacillus subtilis towards Laspartomycin C
by Angelika Diehl, Thomas M. Wood, Susanne Gebhard, Nathaniel I. Martin and Georg Fritz
Antibiotics 2020, 9(11), 729; https://doi.org/10.3390/antibiotics9110729 - 23 Oct 2020
Cited by 6 | Viewed by 3772
Abstract
Cell wall antibiotics are important tools in our fight against Gram-positive pathogens, but many strains become increasingly resistant against existing drugs. Laspartomycin C is a novel antibiotic that targets undecaprenyl phosphate (UP), a key intermediate in the lipid II cycle of cell wall [...] Read more.
Cell wall antibiotics are important tools in our fight against Gram-positive pathogens, but many strains become increasingly resistant against existing drugs. Laspartomycin C is a novel antibiotic that targets undecaprenyl phosphate (UP), a key intermediate in the lipid II cycle of cell wall biosynthesis. While laspartomycin C has been thoroughly examined biochemically, detailed knowledge about potential resistance mechanisms in bacteria is lacking. Here, we use reporter strains to monitor the activity of central resistance modules in the Bacillus subtilis cell envelope stress response network during laspartomycin C attack and determine the impact on the resistance of these modules using knock-out strains. In contrast to the closely related UP-binding antibiotic friulimicin B, which only activates ECF σ factor-controlled stress response modules, we find that laspartomycin C additionally triggers activation of stress response systems reacting to membrane perturbation and blockage of other lipid II cycle intermediates. Interestingly, none of the studied resistance genes conferred any kind of protection against laspartomycin C. While this appears promising for therapeutic use of laspartomycin C, it raises concerns that existing cell envelope stress response networks may already be poised for spontaneous development of resistance during prolonged or repeated exposure to this new antibiotic. Full article
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
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29 pages, 1534 KiB  
Article
Development of an NGS-Based Workflow for Improved Monitoring of Circulating Plasmids in Support of Risk Assessment of Antimicrobial Resistance Gene Dissemination
by Bas Berbers, Pieter-Jan Ceyssens, Pierre Bogaerts, Kevin Vanneste, Nancy H. C. Roosens, Kathleen Marchal and Sigrid C. J. De Keersmaecker
Antibiotics 2020, 9(8), 503; https://doi.org/10.3390/antibiotics9080503 - 11 Aug 2020
Cited by 11 | Viewed by 5479
Abstract
Antimicrobial resistance (AMR) is one of the most prominent public health threats. AMR genes localized on plasmids can be easily transferred between bacterial isolates by horizontal gene transfer, thereby contributing to the spread of AMR. Next-generation sequencing (NGS) technologies are ideal for the [...] Read more.
Antimicrobial resistance (AMR) is one of the most prominent public health threats. AMR genes localized on plasmids can be easily transferred between bacterial isolates by horizontal gene transfer, thereby contributing to the spread of AMR. Next-generation sequencing (NGS) technologies are ideal for the detection of AMR genes; however, reliable reconstruction of plasmids is still a challenge due to large repetitive regions. This study proposes a workflow to reconstruct plasmids with NGS data in view of AMR gene localization, i.e., chromosomal or on a plasmid. Whole-genome and plasmid DNA extraction methods were compared, as were assemblies consisting of short reads (Illumina MiSeq), long reads (Oxford Nanopore Technologies) and a combination of both (hybrid). Furthermore, the added value of conjugation of a plasmid to a known host was evaluated. As a case study, an isolate harboring a large, low-copy mcr-1-carrying plasmid (>200 kb) was used. Hybrid assemblies of NGS data obtained from whole-genome DNA extractions of the original isolates resulted in the most complete reconstruction of plasmids. The optimal workflow was successfully applied to multidrug-resistant Salmonella Kentucky isolates, where the transfer of an ESBL-gene-containing fragment from a plasmid to the chromosome was detected. This study highlights a strategy including wet and dry lab parameters that allows accurate plasmid reconstruction, which will contribute to an improved monitoring of circulating plasmids and the assessment of their risk of transfer. Full article
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
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9 pages, 1227 KiB  
Article
Beta-Lactam Sensitive Bacteria Can Acquire ESBL-Resistance via Conjugation after Long-Term Exposure to Lethal Antibiotic Concentration
by Pilvi Ruotsalainen, Cindy Given, Reetta Penttinen and Matti Jalasvuori
Antibiotics 2020, 9(6), 296; https://doi.org/10.3390/antibiotics9060296 - 2 Jun 2020
Cited by 4 | Viewed by 6340
Abstract
Beta-lactams are commonly used antibiotics that prevent cell-wall biosynthesis. Beta-lactam sensitive bacteria can acquire conjugative resistance elements and hence become resistant even after being exposed to lethal (above minimum inhibitory) antibiotic concentrations. Here we show that neither the length of antibiotic exposure (1 [...] Read more.
Beta-lactams are commonly used antibiotics that prevent cell-wall biosynthesis. Beta-lactam sensitive bacteria can acquire conjugative resistance elements and hence become resistant even after being exposed to lethal (above minimum inhibitory) antibiotic concentrations. Here we show that neither the length of antibiotic exposure (1 to 16 h) nor the beta-lactam type (penam or cephem) have a major impact on the rescue of sensitive bacteria. We demonstrate that an evolutionary rescue can occur between different clinically relevant bacterial species (Klebsiella pneumoniae and Escherichia coli) by plasmids that are commonly associated with extended-spectrum beta-lactamase (ESBL) positive hospital isolates. As such, it is possible that this resistance dynamic may play a role in failing antibiotic therapies in those cases where resistant bacteria may readily migrate into the proximity of sensitive pathogens. Furthermore, we engineered a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-plasmid to encode a guiding CRISPR-RNA against the migrating ESBL-plasmid. By introducing this plasmid into the sensitive bacterium, the frequency of the evolutionarily rescued bacteria decreased by several orders of magnitude. As such, engineering pathogens during antibiotic treatment may provide ways to prevent ESBL-plasmid dispersal and hence resistance evolution. Full article
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
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14 pages, 817 KiB  
Article
Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the lpxD Gene in Acinetobacter baumannii
by Neveen M. Saleh, Marwa S. Hesham, Magdy A. Amin and Reham Samir Mohamed
Antibiotics 2020, 9(4), 164; https://doi.org/10.3390/antibiotics9040164 - 6 Apr 2020
Cited by 12 | Viewed by 4141
Abstract
Acinetobacter baumannii is one of the most common causes of nosocomial infections in intensive care units. Its ability to acquire diverse mechanisms of resistance limits the therapeutic choices for its treatment. This especially concerns colistin, which has been reused recently as a last-resort [...] Read more.
Acinetobacter baumannii is one of the most common causes of nosocomial infections in intensive care units. Its ability to acquire diverse mechanisms of resistance limits the therapeutic choices for its treatment. This especially concerns colistin, which has been reused recently as a last-resort drug against A. baumannii. Here, we explored the impact of gaining colistin resistance on the susceptibility of A. baumannii to other antibiotics and linked colistin resistance acquisition to a gene mutation in A. baumannii. The susceptibility of 95 A. baumannii isolates revealed that 89 isolates were multi-drug resistance (MDR), and nine isolates were resistant to colistin. Subsequently, three isolates, i.e., MS48, MS50, and MS64, exhibited different resistance patterns when colistin resistance was induced and gained resistance to almost all tested antibiotics. Upon TEM examination, morphological alterations were reported for all induced isolates and a colistin-resistant clinical isolate (MS34Col-R) compared to the parental sensitive strains. Finally, genetic alterations in PmrB and LpxACD were assessed, and a point mutation in LpxD was identified in the MS64Col-R and MS34Col-R mutants, corresponding to Lys117Glu substitution in the lipid-binding domain. Our findings shed light on the implications of using colistin in the treatment of A. baumannii, especially at sub-minimum inhibitory concentrations concentrations, since cross-resistance to other classes of antibiotics may emerge, beside the rapid acquisition of resistance against colistin itself due to distinct genetic events. Full article
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
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16 pages, 1291 KiB  
Article
A Novel, Integron-Regulated, Class C β-Lactamase
by Maria-Elisabeth Böhm, Mohammad Razavi, Carl-Fredrik Flach and D. G. Joakim Larsson
Antibiotics 2020, 9(3), 123; https://doi.org/10.3390/antibiotics9030123 - 14 Mar 2020
Cited by 12 | Viewed by 4613
Abstract
AmpC-type β-lactamases severely impair treatment of many bacterial infections, due to their broad spectrum (they hydrolyze virtually all β-lactams, except fourth-generation cephalosporins and carbapenems) and the increasing incidence of plasmid-mediated versions. The original chromosomal AmpCs are often tightly regulated, and their expression is [...] Read more.
AmpC-type β-lactamases severely impair treatment of many bacterial infections, due to their broad spectrum (they hydrolyze virtually all β-lactams, except fourth-generation cephalosporins and carbapenems) and the increasing incidence of plasmid-mediated versions. The original chromosomal AmpCs are often tightly regulated, and their expression is induced in response to exposure to β-lactams. Regulation of mobile ampC expression is in many cases less controlled, giving rise to constitutively resistant strains with increased potential for development or acquisition of additional resistances. We present here the identification of two integron-encoded ampC genes, blaIDC-1 and blaIDC-2 (integron-derived cephalosporinase), with less than 85% amino acid sequence identity to any previously annotated AmpC. While their resistance pattern identifies them as class C β-lactamases, their low isoelectric point (pI) values make differentiation from other β-lactamases by isoelectric focusing impossible. To the best of our knowledge, this is the first evidence of an ampC gene cassette within a class 1 integron, providing a mobile context with profound potential for transfer and spread into clinics. It also allows bacteria to adapt expression levels, and thus reduce fitness costs, e.g., by cassette-reshuffling. Analyses of public metagenomes, including sewage metagenomes, show that the discovered ampCs are primarily found in Asian countries. Full article
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
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Review

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15 pages, 463 KiB  
Review
The Hydric Environment: A Hub for Clinically Relevant Carbapenemase Encoding Genes
by Florence Hammer-Dedet, Estelle Jumas-Bilak and Patricia Licznar-Fajardo
Antibiotics 2020, 9(10), 699; https://doi.org/10.3390/antibiotics9100699 - 15 Oct 2020
Cited by 7 | Viewed by 2692
Abstract
Carbapenems are β-lactams antimicrobials presenting a broad activity spectrum and are considered as last-resort antibiotic. Since the 2000s, carbapenemase producing Enterobacterales (CPE) have emerged and are been quickly globally spreading. The global dissemination of carbapenemase encoding genes (CEG) within clinical relevant bacteria is [...] Read more.
Carbapenems are β-lactams antimicrobials presenting a broad activity spectrum and are considered as last-resort antibiotic. Since the 2000s, carbapenemase producing Enterobacterales (CPE) have emerged and are been quickly globally spreading. The global dissemination of carbapenemase encoding genes (CEG) within clinical relevant bacteria is attributed in part to its location onto mobile genetic elements. During the last decade, carbapenemase producing bacteria have been isolated from non-human sources including the aquatic environment. Aquatic ecosystems are particularly impacted by anthropic activities, which conduce to a bidirectional exchange between aquatic environments and human beings and therefore the aquatic environment may constitute a hub for CPE and CEG. More recently, the isolation of autochtonous aquatic bacteria carrying acquired CEG have been reported and suggest that CEG exchange by horizontal gene transfer occurred between allochtonous and autochtonous bacteria. Hence, aquatic environment plays a central role in persistence, dissemination and emergence of CEG both within environmental ecosystem and human beings, and deserves to be studied with particular attention. Full article
(This article belongs to the Special Issue Microbial Drug Resistance Genes)
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