Scientific article
OA Policy
English

A new mutation in mgrb mediating polymyxin resistance in Klebsiella variicola

Published inInternational journal of antimicrobial agents, vol. 58, no. 5, 106424
Publication date2021-11
First online date2021-08-19
Abstract

Polymyxin resistance is a public health concern – present in humans, animals and the environment – caused by chromosomal-encoding or plasmid-encoding mechanisms. Chromosomal alterations in MgrB are frequently detected in Klebsiella spp., but not yet reported and characterised in Klebsiella variicola (K. variicola). This study performed microbiological and genomic characterisation of three polymyxin-resistant K. variicola isolates (M14, M15 and M50) recovered from the microbiota of migratory birds in Brazil.

The isolates were submitted to SpeI-PFGE, broth microdilution and whole genome sequencing using Illumina MiSeq for analysis of genetic relatedness, sequence typing and detection of antimicrobial-resistance genes. K. variicola isolates belonged to two clones, and susceptibility tests showed resistance only for polymyxins. Sequences of chromosomal two-component systems (PmrAB, PhoPQ, RstAB, CrrAB) and MgrB were evaluated by blastN and blastP against a polymyxin-susceptible K. variicola (A58243), and mutations with biological effect were checked by the PROVEAN tool. K. variicola isolates belonged to two clones, and susceptibility tests showed resistance for polymyxins. In M14 and M15, phoQ deleterious mutations (D90N, I122S and G385S) were identified, while an mgrB variant containing a single deletion (C deletion on position 93) leading to the production of a non-functional protein was detected in M50. mgrB complementation studies showed restoration of polymyxin susceptibility (64 to ≤ 0.25 mg/L) as a wild-type mgrB was inserted into the mgrB-deficient M50.

This study confirmed the role of a non-functional mgrB variant in conferring polymyxin resistance, stressing the role of this regulator in K. variicola and drawing attention to novel polymyxin resistance mechanisms emerging in wildlife.

Keywords
  • Antimicrobial resistance
  • Enterobacterales
  • Migratory birds
  • Two-component systems
  • Animals
  • Anseriformes / microbiology
  • Anti-Bacterial Agents / pharmacology
  • Birds / microbiology
  • Brazil
  • Drug Resistance, Bacterial / genetics
  • Genome, Bacterial / genetics
  • Klebsiella / drug effects
  • Klebsiella / genetics
  • Klebsiella / isolation & purification
  • Membrane Proteins / genetics
  • Microbial Sensitivity Tests
  • Polymyxins / pharmacology
  • Whole Genome Sequencing
Citation (ISO format)
LENZI, Michael H et al. A new mutation in mgrb mediating polymyxin resistance in Klebsiella variicola. In: International journal of antimicrobial agents, 2021, vol. 58, n° 5, p. 106424. doi: 10.1016/j.ijantimicag.2021.106424
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Identifiers
Journal ISSN0924-8579
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95downloads

Technical informations

Creation24/01/2022 13:00:07
First validation04/07/2023 08:47:08
Update time04/07/2023 08:47:08
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