Clinical and laboratory-induced colistin-resistance mechanisms in Acinetobacter baumannii

Christine J Boinett1,2,3, Amy K Cain1,4, Jane Hawkey5,6,7

  • 11​Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Microbial Genomics
|February 6, 2019
PubMed

Insights

Multi-drug resistant Acinetobacter baumannii is a growing threat. Researchers used advanced sequencing to uncover colistin resistance mechanisms, identifying key genes in drug efflux and cell wall synthesis. This reveals how bacteria evade this crucial antibiotic.

Area of Science:

  • Microbiology
  • Genomics
  • Antimicrobial Resistance

Background:

  • Multi-drug resistant (MDR) Acinetobacter baumannii poses a significant global health challenge.
  • Colistin, a vital antibiotic for MDR A. baumannii infections, faces increasing resistance.
  • Understanding colistin resistance mechanisms is crucial for developing effective treatments.

Purpose of the Study:

  • To comprehensively identify the genetic and molecular mechanisms of colistin resistance in Acinetobacter baumannii.
  • To investigate genotypic alterations associated with colistin resistance using high-throughput sequencing.

Main Methods:

  • Transposon-directed insertion site sequencing (TraDIS) to identify essential genes under colistin pressure.
  • RNA sequencing (RNAseq) to analyze gene expression changes in resistant strains.
  • Whole-genome sequencing (WGS) to detect mutations and genetic disruptions in resistant isolates.

Main Results:

  • TraDIS identified genes in drug efflux (adeIJK), phospholipid synthesis (mlaC, mlaF, mlaD), and lipooligosaccharide synthesis (lpxC, lpsO) as critical for colistin survival.
  • RNAseq showed enhanced expression of efflux pump genes (adeI, adeC, emrB, mexB, macAB) in resistant strains.
  • WGS revealed mutations in lipid A synthesis (lpxC), phospholipid synthesis (mlaA), and the BaeS/R two-component system (TCS), with PmrB mutations being primary in Vietnamese clinical strains.

Conclusions:

  • Multiple mechanisms contribute to colistin resistance in A. baumannii, including enhanced drug efflux and alterations in cell envelope synthesis.
  • Gene disruptions or modifications affecting lipid A and phospholipid pathways are key resistance strategies.
  • The study elucidates the full spectrum of colistin resistance mechanisms in A. baumannii, highlighting drug extrusion and lipid A modification.

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