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

Autoři: Natalie A. Mackow aff001;  Juntao Shen aff002;  Mutayyaba Adnan aff001;  Aisha S. Khan aff001;  Bettina C. Fries aff001;  Elizabeth Diago-Navarro aff001
Působiště autorů: Department of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, United States of America aff001;  School of Life Science and Biotechnology, Dalian University of Technology, Dalian, PR China aff002;  Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225131


In the US Carbapenem resistance in Klebsiella pneumoniae (Kp) is primarily attributed to the presence of the genes blaKPC-2 and blaKPC-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 blaKPC plasmids in 7 Kp strains. Furthermore, we show that strains that are unable to acquire blaKPC 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 blaKPC plasmid invasion in a CRISPR-containing Kp strain can be reversed by deleting the CRISPR-cas cassette.

Klíčová slova:

Antibiotic resistance – Antibiotics – CRISPR – Plasmids – Polymerase chain reaction – Repeated sequences – Sequence analysis – Sequence databases


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2019 Číslo 11