Molecular characterization and resistance mechanisms of ertapenem-non-susceptible carbapenem-resistant Klebsiella pneumoniae co-harboring ESBLs or AmpC enzymes with porin loss or efflux pump overexpression

This study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance...

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Vydané v:Journal of bacteriology Ročník 207; číslo 7; s. e0014825
Hlavní autori: Su, Yingying, Zou, Guangmei, Huang, Xin, Bi, Jinli, Meng, Liqin, Zhao, Wei, Li, Taijie
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States American Society for Microbiology 24.07.2025
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Abstract This study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance mechanisms and can aid in controlling CRKP in China.
AbstractList Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates. While carbapenemase-producing CRKP has been extensively studied, the mechanisms underlying resistance in non-carbapenemase-producing CRKP remain less understood. In this study, we investigated 30 ertapenem-resistant non-carbapenemase-producing CRKP clinical isolates. Antimicrobial susceptibility testing revealed multidrug resistance in all strains. Molecular analyses showed that all isolates carried extended-spectrum β-lactamase (ESBL) and/or AmpC β-lactamase genes. Sequencing of outer membrane porin (OMP) genes revealed mutations or deletions in ompK35 and/or ompK36 in the majority of isolates. SDS-PAGE analysis confirmed reduced or absent expression of the corresponding OMP proteins in these strains. Additionally, quantitative PCR showed that several isolates exhibited overexpression of efflux pump genes. These findings indicate that the combined effects of ESBL or AmpC production, porin loss at both the genetic and protein levels, and efflux pump overactivity contribute to ertapenem resistance in non-carbapenemase-producing CRKP. Our results underscore the complexity of resistance mechanisms and highlight the importance of integrated molecular and phenotypic assessments to inform appropriate antimicrobial therapy.Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates. While carbapenemase-producing CRKP has been extensively studied, the mechanisms underlying resistance in non-carbapenemase-producing CRKP remain less understood. In this study, we investigated 30 ertapenem-resistant non-carbapenemase-producing CRKP clinical isolates. Antimicrobial susceptibility testing revealed multidrug resistance in all strains. Molecular analyses showed that all isolates carried extended-spectrum β-lactamase (ESBL) and/or AmpC β-lactamase genes. Sequencing of outer membrane porin (OMP) genes revealed mutations or deletions in ompK35 and/or ompK36 in the majority of isolates. SDS-PAGE analysis confirmed reduced or absent expression of the corresponding OMP proteins in these strains. Additionally, quantitative PCR showed that several isolates exhibited overexpression of efflux pump genes. These findings indicate that the combined effects of ESBL or AmpC production, porin loss at both the genetic and protein levels, and efflux pump overactivity contribute to ertapenem resistance in non-carbapenemase-producing CRKP. Our results underscore the complexity of resistance mechanisms and highlight the importance of integrated molecular and phenotypic assessments to inform appropriate antimicrobial therapy.This study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance mechanisms and can aid in controlling CRKP in China.IMPORTANCEThis study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance mechanisms and can aid in controlling CRKP in China.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates. While carbapenemase-producing CRKP has been extensively studied, the mechanisms underlying resistance in non-carbapenemase-producing CRKP remain less understood. In this study, we investigated 30 ertapenem-resistant non-carbapenemase-producing CRKP clinical isolates. Antimicrobial susceptibility testing revealed multidrug resistance in all strains. Molecular analyses showed that all isolates carried extended-spectrum β-lactamase (ESBL) and/or AmpC β-lactamase genes. Sequencing of outer membrane porin (OMP) genes revealed mutations or deletions in ompK35 and/or ompK36 in the majority of isolates. SDS-PAGE analysis confirmed reduced or absent expression of the corresponding OMP proteins in these strains. Additionally, quantitative PCR showed that several isolates exhibited overexpression of efflux pump genes. These findings indicate that the combined effects of ESBL or AmpC production, porin loss at both the genetic and protein levels, and efflux pump overactivity contribute to ertapenem resistance in non-carbapenemase-producing CRKP. Our results underscore the complexity of resistance mechanisms and highlight the importance of integrated molecular and phenotypic assessments to inform appropriate antimicrobial therapy.IMPORTANCEThis study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance mechanisms and can aid in controlling CRKP in China.
ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates. While carbapenemase-producing CRKP has been extensively studied, the mechanisms underlying resistance in non-carbapenemase-producing CRKP remain less understood. In this study, we investigated 30 ertapenem-resistant non-carbapenemase-producing CRKP clinical isolates. Antimicrobial susceptibility testing revealed multidrug resistance in all strains. Molecular analyses showed that all isolates carried extended-spectrum β-lactamase (ESBL) and/or AmpC β-lactamase genes. Sequencing of outer membrane porin (OMP) genes revealed mutations or deletions in ompK35 and/or ompK36 in the majority of isolates. SDS-PAGE analysis confirmed reduced or absent expression of the corresponding OMP proteins in these strains. Additionally, quantitative PCR showed that several isolates exhibited overexpression of efflux pump genes. These findings indicate that the combined effects of ESBL or AmpC production, porin loss at both the genetic and protein levels, and efflux pump overactivity contribute to ertapenem resistance in non-carbapenemase-producing CRKP. Our results underscore the complexity of resistance mechanisms and highlight the importance of integrated molecular and phenotypic assessments to inform appropriate antimicrobial therapy.IMPORTANCEThis study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance mechanisms and can aid in controlling CRKP in China.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates. While carbapenemase-producing CRKP has been extensively studied, the mechanisms underlying resistance in non-carbapenemase-producing CRKP remain less understood. In this study, we investigated 30 ertapenem-resistant non-carbapenemase-producing CRKP clinical isolates. Antimicrobial susceptibility testing revealed multidrug resistance in all strains. Molecular analyses showed that all isolates carried extended-spectrum β-lactamase (ESBL) and/or AmpC β-lactamase genes. Sequencing of outer membrane porin (OMP) genes revealed mutations or deletions in ompK35 and/or ompK36 in the majority of isolates. SDS-PAGE analysis confirmed reduced or absent expression of the corresponding OMP proteins in these strains. Additionally, quantitative PCR showed that several isolates exhibited overexpression of efflux pump genes. These findings indicate that the combined effects of ESBL or AmpC production, porin loss at both the genetic and protein levels, and efflux pump overactivity contribute to ertapenem resistance in non-carbapenemase-producing CRKP. Our results underscore the complexity of resistance mechanisms and highlight the importance of integrated molecular and phenotypic assessments to inform appropriate antimicrobial therapy.
This study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance mechanisms and can aid in controlling CRKP in China.
Carbapenem-resistant (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates. While carbapenemase-producing CRKP has been extensively studied, the mechanisms underlying resistance in non-carbapenemase-producing CRKP remain less understood. In this study, we investigated 30 ertapenem-resistant non-carbapenemase-producing CRKP clinical isolates. Antimicrobial susceptibility testing revealed multidrug resistance in all strains. Molecular analyses showed that all isolates carried extended-spectrum β-lactamase (ESBL) and/or AmpC β-lactamase genes. Sequencing of outer membrane porin (OMP) genes revealed mutations or deletions in and/or in the majority of isolates. SDS-PAGE analysis confirmed reduced or absent expression of the corresponding OMP proteins in these strains. Additionally, quantitative PCR showed that several isolates exhibited overexpression of efflux pump genes. These findings indicate that the combined effects of ESBL or AmpC production, porin loss at both the genetic and protein levels, and efflux pump overactivity contribute to ertapenem resistance in non-carbapenemase-producing CRKP. Our results underscore the complexity of resistance mechanisms and highlight the importance of integrated molecular and phenotypic assessments to inform appropriate antimicrobial therapy. This study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant (CRKP), involving enzyme-mediated resistance, reduced membrane porin expression, and overactive efflux pumps. These findings provide valuable insights into CRKP resistance mechanisms and can aid in controlling CRKP in China.
Author Bi, Jinli
Zhao, Wei
Huang, Xin
Zou, Guangmei
Li, Taijie
Su, Yingying
Meng, Liqin
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Issue 7
Keywords efflux pump
carbapenemase
carbapenem-resistant Klebsiella pneumonia
mechanisms of drug resistance
outer membrane porin
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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Yingying Su and Guangmei Zou contributed equally to this article. Author order was determined by drawing straws.
The authors declare no conflict of interest.
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SSID ssj0014452
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Snippet This study highlights the complex, multifactorial nature of carbapenem resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP), involving...
Carbapenem-resistant (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates. While...
Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high mortality rates....
ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant challenge in clinical settings due to limited treatment options and high...
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SubjectTerms Anti-Bacterial Agents - pharmacology
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacteriology
beta-Lactamases - genetics
beta-Lactamases - metabolism
carbapenem-resistant Klebsiella pneumonia
Carbapenemase
Carbapenems
Carbapenems - pharmacology
Clinical isolates
Drug Resistance, Multiple, Bacterial
Efflux
efflux pump
Ertapenem
Ertapenem - pharmacology
Gene Expression Regulation, Bacterial
Gene sequencing
Genes
Humans
Klebsiella
Klebsiella Infections - microbiology
Klebsiella pneumoniae
Klebsiella pneumoniae - drug effects
Klebsiella pneumoniae - enzymology
Klebsiella pneumoniae - genetics
Klebsiella pneumoniae - metabolism
mechanisms of drug resistance
Microbial Sensitivity Tests
Multidrug resistance
N-Acetylmuramoyl-L-alanine Amidase - genetics
N-Acetylmuramoyl-L-alanine Amidase - metabolism
outer membrane porin
Porins - genetics
Porins - metabolism
Proteins
Research Article
β Lactamase
Title Molecular characterization and resistance mechanisms of ertapenem-non-susceptible carbapenem-resistant Klebsiella pneumoniae co-harboring ESBLs or AmpC enzymes with porin loss or efflux pump overexpression
URI https://www.ncbi.nlm.nih.gov/pubmed/40511945
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https://www.proquest.com/docview/3234034461
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https://pubmed.ncbi.nlm.nih.gov/PMC12288452
https://doaj.org/article/cca66916e31c49d587ea1896687cc09f
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