Contribution of EmrAB efflux pumps to colistin resistance in Acinetobacter baumannii

J Microbiol. 2017 Feb;55(2):130-136. doi: 10.1007/s12275-017-6408-5. Epub 2017 Jan 26.

Abstract

Efflux pumps play an important role in antimicrobial resistance for Acinetobacter baumannii. However, the function of the Emr pump system and the relationship between Emr and drug resistance has not been characterized in A. baumannii. In this study, four possible groups of emr-like genes were found by searching a genome database. Among them, A1S_1772 (emrB) and A1S_1773 (emrA) were demonstrated to be co-transcribed as a single operon. Moreover, during osmotic stress, A1S_1772 showed the largest change in gene expression compared to the other emrB-like genes, and deletion of A1S_1772 (AB ΔemrB) significantly slowed cell growth in 20% sucrose. Using a phenotypic microarray analysis, the AB ΔemrB mutant was more susceptible to colistin and nafcillin, paromomycin, spiramycin, and D,L-serine hydroxmate than the wild type. The spot assay, time kill assay and minimal inhibition concentration determination also indicated that the wild type could tolerate colistin better than the AB ΔemrB mutant. Finally, the increased expression levels of all emrB-like genes, including A1S_0775, A1S_0909, A1S_1772, and A1S_1799, in colistin resistance-induced A. baumannii further supported the possible involvement of the emrB genes in A. baumannii colistin resistance. Together, the Emr pump systems in A. baumannii contribute to adaptation to osmotic stress and resistance to colistin.

Keywords: Acinetobacter baumannii; antimicrobial resistance; colistin; efflux pump.

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / genetics*
  • Acinetobacter baumannii / growth & development
  • Acinetobacter baumannii / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Colistin / pharmacology*
  • Drug Resistance, Bacterial* / genetics
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Microbial Sensitivity Tests
  • Oligonucleotide Array Sequence Analysis
  • Operon
  • Osmotic Pressure
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Sucrose / pharmacology
  • Transcription, Genetic

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • emrA protein, Bacteria
  • Sucrose
  • Colistin