Prediction of fluoroquinolone susceptibility directly from whole-genome sequence data by using liquid chromatography-tandem mass spectrometry to identify mutant genotypes

Wan Nur Ismah Wan Ahmad Kamil, Yuiko Takebayashi, Jacqueline Findlay, Kate J. Heesom, Juan Carlos Jiménez-Castellanos, Jay Zhang, Lee Graham, Karen Bowker, O. Martin Williams, Alasdair P. MacGowan, Matthew B. Avison*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
241 Downloads (Pure)

Abstract

Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and in vitro mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using Klebsiella pneumoniae as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in K. pneumoniae clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility.

Original languageEnglish
Pages (from-to)e01814-01817
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Antibiotic resistance
  • Klebsiella pneumoniae
  • Susceptibility testing

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