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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin
Antimicrobial Agents and Chemotherapy, Volume 58, No. 8, Year 2014
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Description
A series of colistin-resistant Klebsiella pneumoniae isolates recovered from different countries was investigated in order to evaluate the involvement of the PmrA/PmrB two-component system in this resistance. Six isolates possessed a mutated PmrB protein, which is encoded by the pmrB gene, part of the pmrCAB operon involved in lipopolysaccharide modification. The same amino acid substitution (Thr157Pro) in PmrB was identified in the six isolates. The six isolates belonged to four distinct clonal groups, recovered in South Africa (sequence type 14 [ST14]), Turkey (ST101), and Colombia (ST258 and ST15). Three out of the four clones produced a carbapenemase, OXA-181, OXA-48, or KPC-3, while a single isolate did not produce any carbapenemase. Expression assays revealed an overexpression of the pmrA (70-fold), pmrB (70-fold), pmrC (170-fold), and pmrK (40-fold) genes in the pmrB-mutated isolate compared to expression of the pmrB wild-type isogenic K. pneumoniae isolate, confirming that the PmrB substitution was responsible for increased expression levels of those genes. Complementation assays leading to the expression of a wild-type PmrB protein restored the susceptibility to colistin in all isolates, confirming that the substitution in PmrB was responsible for the resistance phenotype. This study identified a key amino acid located in the PmrB protein as being responsible for the overexpression of pmrCAB and pmrHFIJKLM operons, leading to resistance to colistin. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4136042/bin/supp_58_8_4762__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC4136042/bin/AAC.00084-14_zac008143148so1.pdf
Authors & Co-Authors
Jayol, Aurélie
France, Le Kremlin-bicetre
Résistances Émergentes Aux Antibiotiques
Poirel, Laurent
France, Le Kremlin-bicetre
Résistances Émergentes Aux Antibiotiques
Switzerland, Fribourg
University of Fribourg
Brink, Adrian John
South Africa, Johannesburg
Milpark Hospital
Villegas, María Virginia
Colombia, Cali
Centro Internacional de Entrenamiento e Investigaciones Medicas
Yilmaz, Mesut
Turkey, Istanbul
İstanbul Medipol Üniversitesi
Nordmann, Patrice L.
France, Le Kremlin-bicetre
Résistances Émergentes Aux Antibiotiques
Switzerland, Fribourg
University of Fribourg
Switzerland, Villars-sur-glane
Hopital Cantonal de Fribourg
Statistics
Citations: 166
Authors: 6
Affiliations: 6
Identifiers
Doi:
10.1128/AAC.00084-14
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Genetics And Genomics
Study Locations
South Africa