A novel mutation in pmrB mediates colistin resistance during therapy of Acinetobacter baumannii.
Int J Antimicrob Agents
; 49(6): 727-733, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28438568
ABSTRACT
Acinetobacter baumannii is a highly versatile nosocomial pathogen. Multidrug resistance among A. baumannii isolates led to the use of colistin, subsequently giving rise to colistin-resistant strains. In this study, the genetic and phenotypic profiles of two colistin-resistant A. baumannii isolates were investigated. Two A. baumannii isolates were obtained from Patient 1 (C071 and C440) and three isolates were obtained from Patient 2 (C080, C314 and C428). Susceptibility profiles were determined by VITEK®2 and Etest. Clonality was determined by RAPD analysis and trilocus multiplex PCR. The pmrCAB operon was sequenced and common carbapenemase genes were screened for by PCR. Doubling times, haemolysis, surface motility, biofilm formation, siderophore production and proteolytic activity were phenotypically determined. Finally, whole-genome sequencing was performed for all five isolates. Isolates C440 and C428 were resistant to colistin and were clonally identical to their sensitive counterparts. The cause of colistin resistance was traced to the previously described P233S mutation in pmrB of C440 and to a novel ΔI19 mutation in pmrB of C428. blaOXA-58-like and blaGES-5 from the strains of Patients 1 and 2, respectively, were also detected. C440 had attenuated proteolytic activity and was positive for siderophore production compared with C071. No difference in in vitro virulence was detected between isolates C080, C314 and C428. In conclusion, one common and one novel mutation were encountered in pmrB from two distinct colistin-resistant A. baumannii isolates. These mutations caused colistin resistance during therapy in two distinct clones, and only one of them had altered in vitro virulence.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Fatores de Transcrição
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Infecções por Acinetobacter
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Colistina
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Farmacorresistência Bacteriana
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Acinetobacter baumannii
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Antibacterianos
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Mutação
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article