Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods

J Appl Microbiol. 2016 Sep;121(3):601-17. doi: 10.1111/jam.13169. Epub 2016 Jul 4.

Abstract

A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.

Keywords: acrRAB-TolC; adeABCDFGHIJK; carbapenems; lipid A; mexAB-XY-oprJM; qRT-PCR; whole genome sequencing.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Colistin / pharmacology*
  • Colistin / therapeutic use
  • Drug Resistance, Bacterial*
  • Gram-Negative Bacteria / classification
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Lipid A / metabolism
  • Membrane Transport Proteins / metabolism
  • Microbial Sensitivity Tests
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Minocycline / therapeutic use
  • Mutation
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism
  • RNA, Ribosomal, 16S / genetics
  • RNA, Ribosomal, 16S / metabolism
  • Tigecycline
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Lipid A
  • Membrane Transport Proteins
  • RNA, Bacterial
  • RNA, Ribosomal, 16S
  • Tigecycline
  • beta-Lactamases
  • carbapenemase
  • Minocycline
  • Colistin