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Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae
In the major human pathogen Klebsiella pneumoniae, MgrB inactivation by disruptive insertion sequence (IS) elements and mutations leading to early termination are known to play an important role in polymyxin resistance. In this study, we examined a collection of invasive bla(KPC-2)-producing K. pneu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849082/ https://www.ncbi.nlm.nih.gov/pubmed/35171013 http://dx.doi.org/10.1128/spectrum.01766-21 |
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author | Roch, Mélanie Martins, Willames M. B. S. Sierra, Roberto Gales, Ana C. Andrey, Diego O. |
author_facet | Roch, Mélanie Martins, Willames M. B. S. Sierra, Roberto Gales, Ana C. Andrey, Diego O. |
author_sort | Roch, Mélanie |
collection | PubMed |
description | In the major human pathogen Klebsiella pneumoniae, MgrB inactivation by disruptive insertion sequence (IS) elements and mutations leading to early termination are known to play an important role in polymyxin resistance. In this study, we examined a collection of invasive bla(KPC-2)-producing K. pneumoniae isolates belonging to the high-risk clone sequence type 258 (ST258) displaying high rates of resistance to many antimicrobials, including polymyxins. We identified a deleterious substitution (W20S) in MgrB and confirmed by genetic complementation analysis that this variant was inactive, leading to increased polymyxin B and colistin MICs. IMPORTANCE Carbapenem-resistant Gram-negative bacteria are designated critical pathogens by the World Health Organization. Polymyxins (i.e., polymyxin B and colistin) are last-resort antibiotics and particularly useful against these multidrug-resistant bacteria. In Klebsiella pneumoniae, the inactivation of MgrB, a negative regulator of PhoPQ, was shown to be the major pathway leading to colistin resistance. While gene disruption by insertion sequence (IS) elements and mutations leading to early termination (stop codons) are frequent, deleterious mutations are not observed frequently and have not been characterized. Here, we identified a deleterious substitution (W20S) in MgrB among a collection of bloodstream infection, bla(KPC-2)-producing K. pneumoniae sequence type 258 (ST258) isolates, displaying high rates of resistance to polymyxins and associated with a high mortality rate. The dissemination of such a MgrB-W20S mutation leading to polymyxin resistance within the ST258 high-risk clone background is problematic and thus warrants particular attention. |
format | Online Article Text |
id | pubmed-8849082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88490822022-02-17 Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae Roch, Mélanie Martins, Willames M. B. S. Sierra, Roberto Gales, Ana C. Andrey, Diego O. Microbiol Spectr Observation In the major human pathogen Klebsiella pneumoniae, MgrB inactivation by disruptive insertion sequence (IS) elements and mutations leading to early termination are known to play an important role in polymyxin resistance. In this study, we examined a collection of invasive bla(KPC-2)-producing K. pneumoniae isolates belonging to the high-risk clone sequence type 258 (ST258) displaying high rates of resistance to many antimicrobials, including polymyxins. We identified a deleterious substitution (W20S) in MgrB and confirmed by genetic complementation analysis that this variant was inactive, leading to increased polymyxin B and colistin MICs. IMPORTANCE Carbapenem-resistant Gram-negative bacteria are designated critical pathogens by the World Health Organization. Polymyxins (i.e., polymyxin B and colistin) are last-resort antibiotics and particularly useful against these multidrug-resistant bacteria. In Klebsiella pneumoniae, the inactivation of MgrB, a negative regulator of PhoPQ, was shown to be the major pathway leading to colistin resistance. While gene disruption by insertion sequence (IS) elements and mutations leading to early termination (stop codons) are frequent, deleterious mutations are not observed frequently and have not been characterized. Here, we identified a deleterious substitution (W20S) in MgrB among a collection of bloodstream infection, bla(KPC-2)-producing K. pneumoniae sequence type 258 (ST258) isolates, displaying high rates of resistance to polymyxins and associated with a high mortality rate. The dissemination of such a MgrB-W20S mutation leading to polymyxin resistance within the ST258 high-risk clone background is problematic and thus warrants particular attention. American Society for Microbiology 2022-02-16 /pmc/articles/PMC8849082/ /pubmed/35171013 http://dx.doi.org/10.1128/spectrum.01766-21 Text en Copyright © 2022 Roch 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 | Observation Roch, Mélanie Martins, Willames M. B. S. Sierra, Roberto Gales, Ana C. Andrey, Diego O. Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae |
title | Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae |
title_full | Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae |
title_fullStr | Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae |
title_full_unstemmed | Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae |
title_short | Characterization of Amino Acid Substitution W20S in MgrB Involved in Polymyxin Resistance in Klebsiella pneumoniae |
title_sort | characterization of amino acid substitution w20s in mgrb involved in polymyxin resistance in klebsiella pneumoniae |
topic | Observation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849082/ https://www.ncbi.nlm.nih.gov/pubmed/35171013 http://dx.doi.org/10.1128/spectrum.01766-21 |
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