ISAba1-dependent overexpression of eptA in clinical strains of Acinetobacter baumannii resistant to colistin

J Antimicrob Chemother. 2019 Sep 1;74(9):2544-2550. doi: 10.1093/jac/dkz241.

Abstract

Background: Colistin resistance in Acinetobacter baumannii often results from mutational activation of the two-component system PmrAB and subsequent addition of phospho-ethanolamine (pEtN) to lipooligosaccharide by up-regulated pEtN transferase PmrC.

Objectives: To characterize mechanisms of colistin resistance independent of PmrCAB in A. baumannii.

Methods: Twenty-seven colistin-resistant A. baumannii were collected from 2012 to 2018. Analysis of operon pmrCAB was performed by PCR and sequencing. Seven strains were investigated further by WGS and whole-genome MLST (wgMLST).

Results: Seven out of the 27 selected isolates were found to overexpress eptA, a gene homologous to pmrC, likely as a consequence of upstream insertion of an ISAba1 element. Insertion sites of ISAba1 were mapped 13, 18 and 156 bp ahead of the start codon of eptA in five strains, one strain and one strain, respectively. The finding that the isolates did not cluster together when compared by wgMLST analysis supports the notion that distinct insertion events occurred in close, but different, genetic backgrounds.

Conclusions: Activation of eptA and subsequent addition of pEtN to the cell surface represents a novel mechanism of resistance to colistin in A. baumannii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology*
  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / genetics*
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Colistin / pharmacology*
  • Drug Resistance, Bacterial / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Operon / genetics
  • Transcription Factors / genetics
  • Whole Genome Sequencing

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • PmrB protein, bacteria
  • Transcription Factors
  • pmrA protein, Bacteria
  • Colistin