Journal article
Multifactorial chromosomal variants regulate polymyxin resistance in extensively drug-resistant Klebsiella pneumoniae
ME Pitt, AG Elliot, MD Cao, D Ganesamoorthy, I Karaiskos, H Giamarellou, CS Abboud, MAT Blaskovich, MA Cooper, LJM Coin
Microbial Genomics | MICROBIOLOGY SOC | Published : 2018
Abstract
Extensively drug-resistant Klebsiella pneumoniae (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including 19 polymyxin-resistant and five polymyxin-susceptible strains, were subjected to whole genome sequencing. Seventeen of the 19 polymyxin-resistant isolates harboured variations upstream or within mgrB. The most common mutation identified was an insertion at nucleotide position 75 in mgrB via an ISKpn26-like element in the ST258 lineage and ISKpn13 in one ST11 isolate. Three strains acquired an IS1 element upstream of mgrB an..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
LC is an ARC Future Fellow (FT110100972). MAC is an NHMRC Principal Research Fellow (APP1059354) and currently holds a fractional Professorial Research Fellow appointment at the University of Queensland with his remaining time as CEO of Inflazome Ltd, a company headquartered in Dublin, Ireland, that is developing drugs to address clinical unmet needs in inflammatory disease by targeting the inflammasome. MEP is an Australian Postgraduate Award scholar. AGE and MATB are supported in part by a Wellcome Trust Strategic Award 104797/Z/14/Z. Research was supported by NHMRC grants (APP1005350, APP 1045326), an NIH grant (R21AI098731/R33AI098731) and an AID sequencing Grant (2013) as well as funding from the Institute for Molecular Bioscience Centre for Superbug Solutions (610246).