Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

Abstract

SUMMARY Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.

Evaluation of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Rio Grande do Sul, Brazil

“…and phosphoethanolamine (pEtN), and mgrB gene mutations, responsible for the regulation of the PmrAB and PhoPQ twocomponent systems, as well as through plasmid-mediated mcr-1 gene, responsible for horizontal transfer of colistin resistance, necessitating monitoring of colistin use during therapy and reinforcing control practices during hospital infections to avoid the dissemination of resistance and loss of efficacy of this drug 13 . In the present study, all phenotypic methods (disk diffusion, CN and BC) detected the KPC enzyme activity with 100% sensitivity and specificity.…”

MCR-2-mediated plasmid-borne polymyxin resistance most likely originates from Moraxella pluranimalium

“…[1][2][3] These enzymes have been reported only in Enterobacteriaceae, mainly in Escherichia coli and Klebsiella pneumoniae; however, there have been reports from other enterobacterial genera, including Enterobacter, Salmonella and Shigella. 1 The mcr-1 and mcr-2 genes have both been identified from cattle and pigs. [1][2][3] In addition, the mcr-1 gene has been identified from chickens, 4 but also from river samples and vegetables.…”

“…1 The mcr-1 and mcr-2 genes have both been identified from cattle and pigs. [1][2][3] In addition, the mcr-1 gene has been identified from chickens, 4 but also from river samples and vegetables. 5 MCR-1 and MCR-2, sharing 81% amino acid identity, are phosphoethanolamine transferases of 541 and 538 amino acids, respectively.…”

“…2,3 They add phosphoethanolamine to the lipid A moiety of LPS, leading to a more cationic LPS structure and consequently to resistance to polymyxins. 1 We recently showed that some Moraxella species might constitute putative reservoirs of MCR-like proteins, with corresponding genes located on the chromosome of these species. 6 Hence, MCRlike proteins were identified in Moraxella catarrhalis, Moraxella lincolnii, Moraxella porci and Moraxella osloensis.…”

“…6 Then MICs of colistin were determined for the recombinant strains expressing mcr-1, mcr-2 and mcr-2.2 by broth microdilution (BMD), 1 and this showed that MCR-2.2 conferred exactly the same level of resistance as MCR-1 and MCR-2 (MIC 4 mg/L compared with 0.03 mg/L for the E. coli WT recipient strain), thus showing that the few differences in terms of amino acid sequence did not have an impact on resistance to colistin in E. coli.…”