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Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1
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Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1
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Journal Article
Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1
2019
Overview
Klebsiella pneumoniae
is a major threat to public health with the emergence of isolates resistant to most, if not all, useful antibiotics. We present an in-depth analysis of 178 extended-spectrum beta-lactamase (ESBL)-producing
K. pneumoniae
collected from patients resident in a region of Pakistan, during the period 2010–2012, when the now globally-distributed carbapenemase
bla
-NDM-1 was being acquired by
Klebsiella
. We observed two dominant lineages, but neither the overall resistance profile nor virulence-associated factors, explain their evolutionary success. Phenotypic analysis of resistance shows few differences between the acquisition of resistance genes and the phenotypic resistance profile, including beta-lactam antibiotics that were used to treat ESBL-positive strains. Resistance against these drugs could be explained by inhibitor-resistant beta-lactamase enzymes, carbapenemases or
ampC
type beta-lactamases, at least one of which was detected in most, but not all relevant strains analysed. Complete genomes for six selected strains are reported, these provide detailed insights into the mobile elements present in these isolates during the initial spread of NDM-1. The unexplained success of some lineages within this pool of highly resistant strains, and the discontinuity between phenotypic resistance and genotype at the macro level, indicate that intrinsic mechanisms contribute to competitive advantage and/or resistance.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ beta-Lactamase Inhibitors - pharmacology
/ beta-Lactamase Inhibitors - therapeutic use
/ beta-Lactamases - drug effects
/ Drug Resistance, Multiple, Bacterial - genetics
/ Genomes
/ Humanities and Social Sciences
/ Klebsiella Infections - drug therapy
/ Klebsiella Infections - epidemiology
/ Klebsiella Infections - microbiology
/ Klebsiella pneumoniae - genetics
/ Klebsiella pneumoniae - isolation & purification
/ Klebsiella pneumoniae - pathogenicity
/ Pakistan
/ Science
