Journal article

Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1

Eva Heinz, Hasan Ejaz, Josefin Bartholdson Scott, Nancy Wang, Shruti Gujaran, Derek Pickard, Jonathan Wilksch, Hanwei Cao, Ikram-ul Haq, Gordon Dougan, Richard A Strugnell



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 p..

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Awarded by NHMRC

Awarded by Wellcome Trust

Funding Acknowledgements

The authors thank Karen Oliver for help with the PacBio sequencing, and Andrew Page for helpful discussions on PacBio assembly strategies, Simon Harris for helpful discussions on the manuscript, as well as the Sanger Institute Pathogens Informatics group. We thank Dr. Badr Alzahrani (Jouf University) for comments on the manuscript. This work was supported by the NHMRC (Program Grant 1092262), the Wellcome Trust (206194), and the Higher Education Commission of Pakistan and The Children's Hospital & The ICH, Lahore, Pakistan. H.E. was supported by a scholarship from Higher Education Commission (HEC) Pakistan under the International Research Support Initiative Program (IRSIP). GD is supported by the NIMR Cambridge BRC AMR theme.