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

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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.

Original languageEnglish
Pages (from-to)3035-3042
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume72
Issue number11
DOIs
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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