Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin
View/ Open
Access
info:eu-repo/semantics/openAccessDate
2014Author
Jayol, AureliePoirel, Laurent
Brink, Adrian
Villegas, Maria-Virginia
Yılmaz, Mesut
Nordmann, Patrice
Metadata
Show full item recordCitation
Jayol, A., Poirel, L., Brink, A., Villegas, M. V., Yılmaz, M. ve Nordmann, P. (2014). Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin. Antimicrobial Agents and Chemotherapy, 58(8), 4762,4766. https://dx.doi.org/10.1128/AAC.00084-14Abstract
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.
WoS Q Kategorisi
Q1xmlui.dri2xhtml.METS-1.0.item-scopusquality
Q1Source
Antimicrobial Agents and ChemotherapyVolume
58Issue
8Collections
- Makale Koleksiyonu [3651]
- PubMed İndeksli Yayınlar Koleksiyonu [4050]
- Scopus İndeksli Yayınlar Koleksiyonu [6286]
- WoS İndeksli Yayınlar Koleksiyonu [6433]