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CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae

In the US Carbapenem resistance in Klebsiella pneumoniae (Kp) is primarily attributed to the presence of the genes bla(KPC-2) and bla(KPC-3), which are transmitted via plasmids. Carbapenem-resistant Kp (CR-Kp) infections are associated with hospital outbreaks. They are difficult to treat, and associ...

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Autores principales: Mackow, Natalie A., Shen, Juntao, Adnan, Mutayyaba, Khan, Aisha S., Fries, Bettina C., Diago-Navarro, Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867608/
https://www.ncbi.nlm.nih.gov/pubmed/31747398
http://dx.doi.org/10.1371/journal.pone.0225131
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author Mackow, Natalie A.
Shen, Juntao
Adnan, Mutayyaba
Khan, Aisha S.
Fries, Bettina C.
Diago-Navarro, Elizabeth
author_facet Mackow, Natalie A.
Shen, Juntao
Adnan, Mutayyaba
Khan, Aisha S.
Fries, Bettina C.
Diago-Navarro, Elizabeth
author_sort Mackow, Natalie A.
collection PubMed
description In the US Carbapenem resistance in Klebsiella pneumoniae (Kp) is primarily attributed to the presence of the genes bla(KPC-2) and bla(KPC-3), which are transmitted via plasmids. Carbapenem-resistant Kp (CR-Kp) infections are associated with hospital outbreaks. They are difficult to treat, and associated with high mortality rates prompting studies of how resistance is obtained. In this study, we determined the presence of CRISPR-Cas in 304 clinical Kp strains. The CRISPR-Cas system has been found to prevent the spread of plasmids and bacteriophages, and therefore limits the horizontal gene transfer mediated by these mobile genetic elements. Here, we hypothesized that only those Kp strains that lack CRISPR-Cas can acquire CR plasmids, while those strains that have CRISPR-Cas are protected from gaining these plasmids and thus maintain sensitivity to antimicrobials. Our results show that CRISPR-Cas is absent in most clinical Kp strains including the clinically important ST258 clone. ST258 strains that continue to be sensitive to carbapenems also lack CRISPR-Cas. Interestingly, CRISPR-Cas positive strains, all non-ST258, exhibit lower resistance rates to antimicrobials than CRISPR-Cas negative strains. Importantly, we demonstrate that the presence of CRISPR-Cas appears to inhibit the acquisition of bla(KPC) plasmids in 7 Kp strains. Furthermore, we show that strains that are unable to acquire bla(KPC) plasmids contain CRISPR spacer sequences highly identical to those found in previously published multidrug-resistance-containing plasmids. Lastly, to our knowledge this is the first paper demonstrating that resistance to bla(KPC) plasmid invasion in a CRISPR-containing Kp strain can be reversed by deleting the CRISPR-cas cassette.
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spelling pubmed-68676082019-12-07 CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae Mackow, Natalie A. Shen, Juntao Adnan, Mutayyaba Khan, Aisha S. Fries, Bettina C. Diago-Navarro, Elizabeth PLoS One Research Article In the US Carbapenem resistance in Klebsiella pneumoniae (Kp) is primarily attributed to the presence of the genes bla(KPC-2) and bla(KPC-3), which are transmitted via plasmids. Carbapenem-resistant Kp (CR-Kp) infections are associated with hospital outbreaks. They are difficult to treat, and associated with high mortality rates prompting studies of how resistance is obtained. In this study, we determined the presence of CRISPR-Cas in 304 clinical Kp strains. The CRISPR-Cas system has been found to prevent the spread of plasmids and bacteriophages, and therefore limits the horizontal gene transfer mediated by these mobile genetic elements. Here, we hypothesized that only those Kp strains that lack CRISPR-Cas can acquire CR plasmids, while those strains that have CRISPR-Cas are protected from gaining these plasmids and thus maintain sensitivity to antimicrobials. Our results show that CRISPR-Cas is absent in most clinical Kp strains including the clinically important ST258 clone. ST258 strains that continue to be sensitive to carbapenems also lack CRISPR-Cas. Interestingly, CRISPR-Cas positive strains, all non-ST258, exhibit lower resistance rates to antimicrobials than CRISPR-Cas negative strains. Importantly, we demonstrate that the presence of CRISPR-Cas appears to inhibit the acquisition of bla(KPC) plasmids in 7 Kp strains. Furthermore, we show that strains that are unable to acquire bla(KPC) plasmids contain CRISPR spacer sequences highly identical to those found in previously published multidrug-resistance-containing plasmids. Lastly, to our knowledge this is the first paper demonstrating that resistance to bla(KPC) plasmid invasion in a CRISPR-containing Kp strain can be reversed by deleting the CRISPR-cas cassette. Public Library of Science 2019-11-20 /pmc/articles/PMC6867608/ /pubmed/31747398 http://dx.doi.org/10.1371/journal.pone.0225131 Text en © 2019 Mackow et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mackow, Natalie A.
Shen, Juntao
Adnan, Mutayyaba
Khan, Aisha S.
Fries, Bettina C.
Diago-Navarro, Elizabeth
CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae
title CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae
title_full CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae
title_fullStr CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae
title_full_unstemmed CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae
title_short CRISPR-Cas influences the acquisition of antibiotic resistance in Klebsiella pneumoniae
title_sort crispr-cas influences the acquisition of antibiotic resistance in klebsiella pneumoniae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867608/
https://www.ncbi.nlm.nih.gov/pubmed/31747398
http://dx.doi.org/10.1371/journal.pone.0225131
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