کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5528707 | 1548304 | 2017 | 9 صفحه PDF | دانلود رایگان |
- Three multidrug resistant A. baumannii (MDR-AB) strains were identified, as hypermutator.
- Three hypermutator strains belonged to distinct clones.
- A hypermutator strain had three differentially expressed proteins with sizes of 51.2, 20.9, and 11.9Â kDa.
BackgroundThe emergence of multidrug resistant Acinetobacter baumannii within hospitals poses a significant threat to patients. The inherent rate of mutation of these strains has not been described nor has the mechanism by which drug resistance arises.MethodsHere, we determined the spontaneous mutation rates in 93 clinical strains of A. baumannii using fluctuation analysis. To rule out the clonal relatedness of hypermutator strains, pulsed-field gel electrophoresis (PFGE) was conducted. Using a combination of two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry, the differentially expressed proteins of a hypermutator and a reference strain were identified.ResultsThe spontaneous mutation rate of multi-drug resistant A. baumannii strains varied broadly from 0 to 2.1Â ÃÂ 10â6 mutation per cell division. The mutation rate in three multidrug resistant A. baumannii (MDR-AB) strains was found to be 1.63Â ÃÂ 10â6 (95% confidence interval (CI): 1Â ÃÂ 10â6-2Â ÃÂ 10â6), 2.1Â ÃÂ 10â6 (95% CI: 2Â ÃÂ 10â6 â 3Â ÃÂ 10â6), and 1.78Â ÃÂ 10â8 (95% CI: 9.29Â ÃÂ 10â9 2.95Â ÃÂ 10â8), consistent with a hypermutator phenotype. This rate is approximately 1000-fold higher than the average mutation rate in other MDR-ABs. PFGE of the three hypermutator strains indicate that they belong to distinct clones. Proteomic analysis of one hypermutator strain revealed 31 differentially expressed proteins including three with sizes of 51.2, 20.9, and 11.9Â kDa, which corresponded to a serine protease, a polyisoprenoid-binding protein, and the peptidoglycan binding protein, LysM. The serine protease was expressed only in the hypermutator strain, whereas the polyisoprenoid-binding protein and the peptidoglycan binding protein LysM were down-regulated 1.6 and 3-fold, respectively, in the hypermutators strain.ConclusionHypermutator A. baumannii strains occur with a low, but appreciable frequency among clinical multi-drug resistant isolates. The presence of hypermutator clinical isolates raises concerns that they may contribute to the failure of antibiotic treatment in infected patients and confound the interpretation of in vitro antibiotic susceptibility testing. The differentially expressed proteins involved in biofilm suppression and oxidative stress response, may represent adaptations derived from the hypermutator phenotype, a hypothesis that needs further testing.
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volumes 800â802, August 2017, Pages 37-45