Modulation of mgrB gene expression as a source of colistin resistance in Klebsiella oxytoca

Int J Antimicrob Agents. 2015 Jul;46(1):108-10. doi: 10.1016/j.ijantimicag.2015.02.015. Epub 2015 Mar 28.


Gene modifications in the PmrAB and PhoPQ two-component regulatory systems, as well as inactivation of the mgrB gene, are known to be causes of colistin resistance in Klebsiella pneumoniae. The objective of this study was to characterise the mechanism involved in colistin resistance in a Klebsiella oxytoca isolate. A K. oxytoca clinical isolate showing resistance to colistin was recovered in Cali, Colombia. The pmrA, pmrB, phoP, phoQ and mgrB genes were amplified and sequenced. Wild-type mgrB genes from K. pneumoniae and K. oxytoca were cloned, and corresponding recombinant plasmids were used for complementation assays. By analysing the mgrB gene of the K. oxytoca isolate and its flanking sequences, an insertion sequence (IS) of 1196bp was identified in its promoter region. The insertion was located between nucleotides -39 and -38 when referring to the start codon of the mgrB gene, thus negatively interfering with expression of the mgrB gene by modifying its promoter structure. This IS was very similar to ISKpn26 (99% nucleotide identity) belonging to the IS5 family. Complementation assays with mgrB genes from wild-type K. pneumoniae or K. oxytoca restored full susceptibility to colistin. In conclusion, here we identified the mechanism involved in colistin resistance in a K. oxytoca isolate. Modulation of mgrB gene expression was the key factor for this acquired resistance to colistin.

Keywords: PhoPQ regulatory system; Polymyxin; Resistance.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / pharmacology*
  • Cloning, Molecular
  • Colistin / pharmacology*
  • Colombia
  • DNA Transposable Elements
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial*
  • Gene Expression*
  • Genetic Complementation Test
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella oxytoca / drug effects*
  • Klebsiella oxytoca / genetics*
  • Klebsiella oxytoca / isolation & purification
  • Klebsiella oxytoca / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Plasmids
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA


  • Anti-Bacterial Agents
  • DNA Transposable Elements
  • DNA, Bacterial
  • Membrane Proteins
  • Colistin

Associated data

  • GENBANK/KP748172