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High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae

Klebsiella pneumoniae is a pathogen known for its high frequency of antimicrobial resistance. Responses to various environmental stresses during its life can influence the resistance to antibiotics. Here, we demonstrate the role and mechanism of KbvR regulator in the response to environmental osmoti...

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Autores principales: Wang, Meng, Tian, Yujiao, Xu, Li, Zhang, Fusheng, Lu, Huigai, Li, Moran, Li, Bei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241633/
https://www.ncbi.nlm.nih.gov/pubmed/35658577
http://dx.doi.org/10.1128/spectrum.00507-22
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author Wang, Meng
Tian, Yujiao
Xu, Li
Zhang, Fusheng
Lu, Huigai
Li, Moran
Li, Bei
author_facet Wang, Meng
Tian, Yujiao
Xu, Li
Zhang, Fusheng
Lu, Huigai
Li, Moran
Li, Bei
author_sort Wang, Meng
collection PubMed
description Klebsiella pneumoniae is a pathogen known for its high frequency of antimicrobial resistance. Responses to various environmental stresses during its life can influence the resistance to antibiotics. Here, we demonstrate the role and mechanism of KbvR regulator in the response to environmental osmotic stress and in the effect of osmotic stress on antimicrobial resistance. The kbvR mutant strain exhibited increasing tolerance to high osmotic stress and certain antibiotics, including β-lactams. The expression levels of KbvR and outer membrane porin OmpK36 were upregulated in response to high osmotic stress in the wild type (WT), and the deletion of kbvR decreased the expression level of ompK36. The membrane permeability of the kbvR mutant strain was decreased, which was partly restored through the upregulated expression of OmpK36. The DNA affinity purification sequencing (DAP-seq) and microscale thermophoresis (MST) assay disclosed the binding of KbvR to the promoter of the ompK36 gene, indicating that KbvR directly and positively regulated the expression of OmpK36. The high osmotic stress increased the susceptibility to β-lactams and the expression of ompK36 in the WT strain. However, the increased ompK36 expression and the susceptibility to β-lactams in the kbvR mutant strain under high osmotic stress were lower than those of WT. In conclusion, our study has identified that high osmotic stress in the environment influenced the resistance of K. pneumoniae to antibiotics and that the regulation of KbvR with OmpR on the expression of OmpK36 was involved in countering high osmotic stress to change the antimicrobial resistance. IMPORTANCE Klebsiella pneumoniae is considered a global threat because of the rising prevalence of multidrug-resistant strains and their optimal adaptation to clinical environments and the human host. The sensing and adaption abilities of bacteria to the environmental osmotic stress can change the expression of their outer membrane porins, membrane permeability, and resistance to antibiotics. This study reports that KbvR is a newly found regulator that can be upregulated under high osmotic stress and directly regulate the expression of OmpK36 to change the resistance of K. pneumoniae to β-lactam antibiotics. The results demonstrate how adaptation to high osmotic stress changes the sensitivity of K. pneumoniae to antibiotics. The mechanism can be used to sensitize bacteria to antibiotics and highlight new potential strategies for exploiting shared constraints in governing adaptation to diverse environmental challenges.
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spelling pubmed-92416332022-06-30 High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae Wang, Meng Tian, Yujiao Xu, Li Zhang, Fusheng Lu, Huigai Li, Moran Li, Bei Microbiol Spectr Research Article Klebsiella pneumoniae is a pathogen known for its high frequency of antimicrobial resistance. Responses to various environmental stresses during its life can influence the resistance to antibiotics. Here, we demonstrate the role and mechanism of KbvR regulator in the response to environmental osmotic stress and in the effect of osmotic stress on antimicrobial resistance. The kbvR mutant strain exhibited increasing tolerance to high osmotic stress and certain antibiotics, including β-lactams. The expression levels of KbvR and outer membrane porin OmpK36 were upregulated in response to high osmotic stress in the wild type (WT), and the deletion of kbvR decreased the expression level of ompK36. The membrane permeability of the kbvR mutant strain was decreased, which was partly restored through the upregulated expression of OmpK36. The DNA affinity purification sequencing (DAP-seq) and microscale thermophoresis (MST) assay disclosed the binding of KbvR to the promoter of the ompK36 gene, indicating that KbvR directly and positively regulated the expression of OmpK36. The high osmotic stress increased the susceptibility to β-lactams and the expression of ompK36 in the WT strain. However, the increased ompK36 expression and the susceptibility to β-lactams in the kbvR mutant strain under high osmotic stress were lower than those of WT. In conclusion, our study has identified that high osmotic stress in the environment influenced the resistance of K. pneumoniae to antibiotics and that the regulation of KbvR with OmpR on the expression of OmpK36 was involved in countering high osmotic stress to change the antimicrobial resistance. IMPORTANCE Klebsiella pneumoniae is considered a global threat because of the rising prevalence of multidrug-resistant strains and their optimal adaptation to clinical environments and the human host. The sensing and adaption abilities of bacteria to the environmental osmotic stress can change the expression of their outer membrane porins, membrane permeability, and resistance to antibiotics. This study reports that KbvR is a newly found regulator that can be upregulated under high osmotic stress and directly regulate the expression of OmpK36 to change the resistance of K. pneumoniae to β-lactam antibiotics. The results demonstrate how adaptation to high osmotic stress changes the sensitivity of K. pneumoniae to antibiotics. The mechanism can be used to sensitize bacteria to antibiotics and highlight new potential strategies for exploiting shared constraints in governing adaptation to diverse environmental challenges. American Society for Microbiology 2022-06-06 /pmc/articles/PMC9241633/ /pubmed/35658577 http://dx.doi.org/10.1128/spectrum.00507-22 Text en Copyright © 2022 Wang et al. 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 (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Wang, Meng
Tian, Yujiao
Xu, Li
Zhang, Fusheng
Lu, Huigai
Li, Moran
Li, Bei
High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae
title High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae
title_full High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae
title_fullStr High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae
title_full_unstemmed High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae
title_short High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae
title_sort high osmotic stress increases ompk36 expression through the regulation of kbvr to decrease the antimicrobial resistance of klebsiella pneumoniae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241633/
https://www.ncbi.nlm.nih.gov/pubmed/35658577
http://dx.doi.org/10.1128/spectrum.00507-22
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