Antimicrobial Resistance Mechanisms in Bacteria

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 13980

Special Issue Editors


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Guest Editor
State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia
Interests: molecular mechanisms of antimicrobial resistance; horizontal gene transfer; gene expression

E-Mail Website
Guest Editor
State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia
Interests: nosocomial infections; genotyping; MRSA; resistance to antimicrobials

E-Mail Website
Guest Editor
State Research Center for Applied Microbiology & Biotechnology, 142279 Obolensk, Russia
Interests: whole genome analysis; plasmids; resistance and virulence genes; genomic islands

Special Issue Information

Dear Colleagues,

Gram-negative bacteria are prevalent pathogens associated with hospital-acquired infections that are a major challenge for patient safety, especially in ICUs. The growing number of antimicrobial-resistant (AMR) pathogens places a significant burden on healthcare systems. Even multi-drug (MDR), extensive-drug (XDR), and pan-drug (PDR) resistant bacteria have developed because of horizontal transfer (HGT) of AMR genes. HGT through plasmids plays a major role. Typing of the plasmids and study of their spread and evolution in different bacterial hosts provide knowledge concerning the transmission of AMR.

The aim of this Special Issue is to provide a collection of articles that highlight the current issues in the research of “Plasmids Carrying Antimicrobial Resistance Genes in Gram-Negative Bacteria”. As the Guest Editor, I invite you to submit research articles, review articles, and short communications dedicated to the AMR genes and plasmids in Gram-negative bacteria, plasmid typing, HGT from the human microbiome or animal pathogens, etc.

Dr. Nadezhda Fursova
Dr. Olga Khokhlova
Dr. Angelina Kislichkina
Guest Editors

Manuscript Submission Information

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Keywords

  • antimicrobial resistance
  • AMR
  • MDR
  • resistance genes
  • gram-negative bacteria
  • plasmids
  • horizontal gene transfer
  • HGT
  • incompatibility groups
  • Inc groups

Published Papers (7 papers)

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Editorial

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2 pages, 166 KiB  
Editorial
Plasmids Carrying Antimicrobial Resistance Genes in Gram-Negative Bacteria
by Nadezhda K. Fursova, Angelina A. Kislichkina and Olga E. Khokhlova
Microorganisms 2022, 10(8), 1678; https://doi.org/10.3390/microorganisms10081678 - 20 Aug 2022
Cited by 6 | Viewed by 1265
Abstract
Gram-negative bacteria are prevalent pathogens associated with hospital-acquired infections (HAI) that are a major challenge for patient safety, especially in intensive care units [...] Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)

Research

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14 pages, 3166 KiB  
Article
Role of the Bacterial Amyloid-like Hfq in Fluoroquinolone Fluxes
by Florian Turbant, Emeline Esnouf, Francois Rosaz, Frank Wien, Grzegorz Węgrzyn, Hugo Chauvet and Véronique Arluison
Microorganisms 2024, 12(1), 53; https://doi.org/10.3390/microorganisms12010053 - 28 Dec 2023
Viewed by 774
Abstract
Due to their two-cell membranes, Gram-negative bacteria are particularly resistant to antibiotics. Recent investigations aimed at exploring new target proteins involved in Gram-negative bacteria adaptation helped to identify environmental changes encountered during infection. One of the most promising approaches in finding novel targets [...] Read more.
Due to their two-cell membranes, Gram-negative bacteria are particularly resistant to antibiotics. Recent investigations aimed at exploring new target proteins involved in Gram-negative bacteria adaptation helped to identify environmental changes encountered during infection. One of the most promising approaches in finding novel targets for antibacterial drugs consists of blocking noncoding RNA-based regulation using the protein cofactor, Hfq. Although Hfq is important in many bacterial pathogens, its involvement in antibiotics response is still unclear. Indeed, Hfq may mediate drug resistance by regulating the major efflux system in Escherichia coli, but it could also play a role in the influx of antibiotics. Here, using an imaging approach, we addressed this problem quantitatively at the single-cell level. More precisely, we analyzed how Hfq affects the dynamic influx and efflux of ciprofloxacin, an antibiotic from the group of fluoroquinolones that is used to treat bacterial infections. Our results indicated that the absence of either whole Hfq or its C-terminal domain resulted in a more effective accumulation of ciprofloxacin, irrespective of the presence of the functional AcrAB-TolC efflux pump. However, overproduction of the MicF small regulatory RNA, which reduces the efficiency of expression of the ompF gene (coding for a porin involved in antibiotics influx) in a Hfq-dependent manner, resulted in impaired accumulation of ciprofloxacin. These results led us to propose potential mechanisms of action of Hfq in the regulation of fluoroquinolone fluxes across the E. coli envelope. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)
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17 pages, 2053 KiB  
Article
Whole-Genome Sequencing Revealed the Fusion Plasmids Capable of Transmission and Acquisition of Both Antimicrobial Resistance and Hypervirulence Determinants in Multidrug-Resistant Klebsiella pneumoniae Isolates
by Andrey Shelenkov, Yulia Mikhaylova, Shushanik Voskanyan, Anna Egorova and Vasiliy Akimkin
Microorganisms 2023, 11(5), 1314; https://doi.org/10.3390/microorganisms11051314 - 17 May 2023
Viewed by 1468
Abstract
Klebsiella pneumoniae, a member of the Enterobacteriaceae family, has become a dangerous pathogen accountable for a large fraction of the various infectious diseases in both clinical and community settings. In general, the K. pneumoniae population has been divided into the so-called classical [...] Read more.
Klebsiella pneumoniae, a member of the Enterobacteriaceae family, has become a dangerous pathogen accountable for a large fraction of the various infectious diseases in both clinical and community settings. In general, the K. pneumoniae population has been divided into the so-called classical (cKp) and hypervirulent (hvKp) lineages. The former, usually developing in hospitals, can rapidly acquire resistance to a wide spectrum of antimicrobial drugs, while the latter is associated with more aggressive but less resistant infections, mostly in healthy humans. However, a growing number of reports in the last decade have confirmed the convergence of these two distinct lineages into superpathogen clones possessing the properties of both, and thus imposing a significant threat to public health worldwide. This process is associated with horizontal gene transfer, in which plasmid conjugation plays a very important role. Therefore, the investigation of plasmid structures and the ways plasmids spread within and between bacterial species will provide benefits in developing prevention measures against these powerful pathogens. In this work, we investigated clinical multidrug-resistant K. pneumoniae isolates using long- and short-read whole-genome sequencing, which allowed us to reveal fusion IncHI1B/IncFIB plasmids in ST512 isolates capable of simultaneously carrying hypervirulence (iucABCD, iutA, prmpA, peg-344) and resistance determinants (armA, blaNDM-1 and others), and to obtain insights into their formation and transmission mechanisms. Comprehensive phenotypic, genotypic and phylogenetic analysis of the isolates, as well as of their plasmid repertoire, was performed. The data obtained will facilitate epidemiological surveillance of high-risk K. pneumoniae clones and the development of prevention strategies against them. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)
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16 pages, 3923 KiB  
Article
High-Molecular-Weight Plasmids Carrying Carbapenemase Genes blaNDM-1, blaKPC-2, and blaOXA-48 Coexisting in Clinical Klebsiella pneumoniae Strains of ST39
by Ekaterina S. Kuzina, Angelina A. Kislichkina, Angelika A. Sizova, Yury P. Skryabin, Tatiana S. Novikova, Olga N. Ershova, Ivan A. Savin, Olga E. Khokhlova, Alexander G. Bogun and Nadezhda K. Fursova
Microorganisms 2023, 11(2), 459; https://doi.org/10.3390/microorganisms11020459 - 11 Feb 2023
Cited by 3 | Viewed by 1926
Abstract
Background: Klebsiella pneumoniae, a member of the ESKAPE group of bacterial pathogens, has developed multi-antimicrobial resistance (AMR), including resistance to carbapenems, which has increased alarmingly due to the acquisition of carbapenemase genes located on specific plasmids. Methods: Four clinical K. pneumoniae isolates were collected [...] Read more.
Background: Klebsiella pneumoniae, a member of the ESKAPE group of bacterial pathogens, has developed multi-antimicrobial resistance (AMR), including resistance to carbapenems, which has increased alarmingly due to the acquisition of carbapenemase genes located on specific plasmids. Methods: Four clinical K. pneumoniae isolates were collected from four patients of a neuro-intensive care unit in Moscow, Russia, during the point prevalence survey. The AMR phenotype was estimated using the Vitec-2 instrument, and whole genome sequencing (WGS) was done using Illumina and Nanopore technologies. Results: All strains were resistant to beta-lactams, nitrofurans, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines. WGS analysis revealed that all strains were closely related to K. pneumoniae ST39, capsular type K-23, with 99.99% chromosome identity. The novelty of the study is the description of the strains carrying simultaneously three large plasmids of the IncHI1B, IncC, and IncFIB groups carrying the carbapenemase genes of three types, blaOXA-48, blaNDM-1, and blaKPC-2, respectively. The first of them, highly identical in all strains, was a hybrid plasmid that combined two regions of the resistance genes (blaOXA-48 and blaTEM-1 + blaCTX-M-15 + blaOXA-1 + catB + qnrS1 + int1) and a region of the virulence genes (iucABCD, iutA, terC, and rmpA2::IS110). Conclusion: The spread of K. pneumoniae strains carrying multiple plasmids conferring resistance even to last-resort antibiotics is of great clinical concern. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)
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15 pages, 1825 KiB  
Article
Molecular Epidemiology of mcr-1-Positive Escherichia coli and Klebsiella pneumoniae Isolates: Results from Russian Sentinel Surveillance (2013–2018)
by Valeria Shapovalova, Elvira Shaidullina, Ilya Azizov, Eugene Sheck, Alexey Martinovich, Marina Dyachkova, Alina Matsvay, Yulia Savochkina, Kamil Khafizov, Roman Kozlov, German Shipulin and Mikhail Edelstein
Microorganisms 2022, 10(10), 2034; https://doi.org/10.3390/microorganisms10102034 - 14 Oct 2022
Cited by 2 | Viewed by 1676
Abstract
Background: The dissemination of mobile colistin resistance (mcr) genes is a serious healthcare threat because polymyxins represent “last-line” therapeutics for multi-drug-resistant Gram-negative pathogens. This study aimed to assess the prevalence of colistin resistance and mcr genes and characteristics of clinical Escherichia [...] Read more.
Background: The dissemination of mobile colistin resistance (mcr) genes is a serious healthcare threat because polymyxins represent “last-line” therapeutics for multi-drug-resistant Gram-negative pathogens. This study aimed to assess the prevalence of colistin resistance and mcr genes and characteristics of clinical Escherichia coli (Eco) and Klebsiella pneumoniae (Kpn) isolates and plasmids carrying these genes in Russia. Methods: A total of 4324 Eco and 4530 Kpn collected in the frame of sentinel surveillance in 2013–2018 were tested for susceptibility to colistin and other antibiotics using the broth microdilution method. mcr genes were screened by real-time PCR. Phylogeny, genomic features and plasmids of mcr-positive isolates were assessed using whole-genome sequencing and subsequent bioinformatic analysis. Results: Colistin resistance was detected in 2.24% Eco and 9.3% Kpn. Twenty-two (0.51%) Eco and two (0.04%) Kpn from distant sites carried mcr-1.1. Most mcr-positive isolates co-harbored ESBLs and other resistance determinants to various antibiotic classes. The mcr-positive Eco belonged to 16 MLST types, with ST359 being most common; Kpn belonged to ST307 and ST23. mcr-1.1 was carried mainly in IncI2 (n = 18) and IncX4 (n = 5) plasmids highly similar to those identified previously in human, animal and environmental isolates. Conclusion: This study demonstrated a dissemination of “typical” mcr-bearing plasmids among diverse Eco and Kpn genotypes and across a wide geographic area in Russia. Given the frequent association of mcr with other resistance determinants and potential clinical impact, the continual surveillance of this threat is warranted. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)
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11 pages, 2138 KiB  
Article
Emergence and Transfer of Plasmid-Harbored rmtB in a Clinical Multidrug-Resistant Pseudomonas aeruginosa Strain
by Jiacong Gao, Xiaoya Wei, Liwen Yin, Yongxin Jin, Fang Bai, Zhihui Cheng and Weihui Wu
Microorganisms 2022, 10(9), 1818; https://doi.org/10.3390/microorganisms10091818 - 11 Sep 2022
Cited by 3 | Viewed by 1373
Abstract
Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a great challenge to clinical treatment. In this study, we characterized a ST768 MDR P. aeruginosa strain, Pa150, that was isolated from a diabetic foot patient. The minimum inhibitory concentration (MIC) assay showed that Pa150 was resistant to [...] Read more.
Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a great challenge to clinical treatment. In this study, we characterized a ST768 MDR P. aeruginosa strain, Pa150, that was isolated from a diabetic foot patient. The minimum inhibitory concentration (MIC) assay showed that Pa150 was resistant to almost all kinds of antibiotics, especially aminoglycosides. Whole genome sequencing revealed multiple antibiotic resistant genes on the chromosome and a 437-Kb plasmid (named pTJPa150) that harbors conjugation-related genes. A conjugation assay verified its self-transmissibility. On the pTJPa150 plasmid, we identified a 16S rRNA methylase gene, rmtB, that is flanked by mobile genetic elements (MGEs). The transfer of the pTJPa150 plasmid or the cloning of the rmtB gene into the reference strain, PAO1, significantly increased the bacterial resistance to aminoglycoside antibiotics. To the best of our knowledge, this is the first report of an rmtB-carrying conjugative plasmid isolated from P. aeruginosa, revealing a novel possible transmission mechanism of the rmtB gene. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)
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Review

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26 pages, 1002 KiB  
Review
A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques
by Oznur Caliskan-Aydogan and Evangelyn C. Alocilja
Microorganisms 2023, 11(6), 1491; https://doi.org/10.3390/microorganisms11061491 - 03 Jun 2023
Cited by 9 | Viewed by 4518
Abstract
Infectious disease outbreaks have caused thousands of deaths and hospitalizations, along with severe negative global economic impacts. Among these, infections caused by antimicrobial-resistant microorganisms are a major growing concern. The misuse and overuse of antimicrobials have resulted in the emergence of antimicrobial resistance [...] Read more.
Infectious disease outbreaks have caused thousands of deaths and hospitalizations, along with severe negative global economic impacts. Among these, infections caused by antimicrobial-resistant microorganisms are a major growing concern. The misuse and overuse of antimicrobials have resulted in the emergence of antimicrobial resistance (AMR) worldwide. Carbapenem-resistant Enterobacterales (CRE) are among the bacteria that need urgent attention globally. The emergence and spread of carbapenem-resistant bacteria are mainly due to the rapid dissemination of genes that encode carbapenemases through horizontal gene transfer (HGT). The rapid dissemination enables the development of host colonization and infection cases in humans who do not use the antibiotic (carbapenem) or those who are hospitalized but interacting with environments and hosts colonized with carbapenemase-producing (CP) bacteria. There are continuing efforts to characterize and differentiate carbapenem-resistant bacteria from susceptible bacteria to allow for the appropriate diagnosis, treatment, prevention, and control of infections. This review presents an overview of the factors that cause the emergence of AMR, particularly CRE, where they have been reported, and then, it outlines carbapenemases and how they are disseminated through humans, the environment, and food systems. Then, current and emerging techniques for the detection and surveillance of AMR, primarily CRE, and gaps in detection technologies are presented. This review can assist in developing prevention and control measures to minimize the spread of carbapenem resistance in the human ecosystem, including hospitals, food supply chains, and water treatment facilities. Furthermore, the development of rapid and affordable detection techniques is helpful in controlling the negative impact of infections caused by AMR/CRE. Since delays in diagnostics and appropriate antibiotic treatment for such infections lead to increased mortality rates and hospital costs, it is, therefore, imperative that rapid tests be a priority. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Mechanisms in Bacteria)
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