July 7, 2019  |  

Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae.

Authors: Leung, Lisa M and Cooper, Vaughn S and Rasko, David A and Guo, Qinglan and Pacey, Marissa P and McElheny, Christi L and Mettus, Roberta T and Yoon, Sung Hwan and Goodlett, David R and Ernst, Robert K and Doi, Yohei

Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited.To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.The strains were subjected to high-throughput sequencing with Illumina HiSeq. The mgrB gene was amplified by PCR and sequenced. Lipid profiles were determined using MALDI-TOF MS.All patients were treated with colistimethate prior to the isolation of colistin-resistant strains (MIC >2?mg/L). Seven of 11 colistin-resistant strains had deletion or insertional inactivation of mgrB. Three strains, including one with an mgrB deletion, had non-synonymous pmrB mutations associated with colistin resistance. When analysed by MALDI-TOF MS, all colistin-resistant strains generated mass spectra containing ions at m/z 1955 and 1971, consistent with addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A, whereas only one of the susceptible strains displayed this lipid A phenotype.The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: [email protected]

Journal: The Journal of antimicrobial chemotherapy
DOI: 10.1093/jac/dkx234
Year: 2017

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