Mutations in the pmrB gene constitute the major mechanism underlying chromosomally encoded colistin resistance in clinical Escherichia coli.

Autor: Lin JC; Division of Infectious Diseases and Tropical Medicine, Department of Internal, Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Kristopher Siu LK; Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan., Chang FY; Division of Infectious Diseases and Tropical Medicine, Department of Internal, Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Wang CH; Division of Infectious Diseases and Tropical Medicine, Department of Internal, Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: sasak0308@gmail.com.
Jazyk: angličtina
Zdroj: Journal of global antimicrobial resistance [J Glob Antimicrob Resist] 2024 Sep; Vol. 38, pp. 275-280. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1016/j.jgar.2024.06.013
Abstrakt: Objectives: The mechanisms underlying chromosomally encoded colistin resistance in Escherichia coli remain insufficiently investigated. In this study, we investigated the contribution of various pmrB mutations from E. coli clinical isolates to colistin resistance.
Methods: The resistance mechanisms in eight mcr-negative colistin-resistant E. coli isolates obtained from a nationwide surveillance program in Taiwan using recombinant DNA techniques and complementary experiments were investigated. The minimal inhibitory concentrations (MICs) of colistin in the recombinant strains were compared with those in the parental strains. The expression levels of pmrA and pmrK (which are part of the pmrCAB and pmrHFIJKLM operons associated with colistin resistance) were measured using reverse transcription-quantitative real-time polymerase chain reaction.
Results: In the complementation experiments, various mutated pmrB alleles from the eight mcr-negative colistin-resistant E. coli strains were introduced into an ATCC25922 mutant with a PmrB deletion, which resulted in colistin resistance. The MIC levels of colistin in the most complemented strains were comparable to those of the parental colistin-resistant strains. Increased expression levels of pmrA and pmrK were consistently detected in most complemented strains. The impact for colistin resistance was confirmed for various novel amino acid substitutions, P94L, G19E, L194P, L98R and R27L in PmrB from the parental clinical strains. The detected amino acid substitutions are distributed in the different functional domains of PmrB.
Conclusions: Colistin resistance mediated by amino acid substitutions in PmrB is a major chromosomally encoded mechanism in E. coli of clinical origin.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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