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Acinetobacter baumannii is a nosocomial pathogen and causes infections in hospitals worldwide. This organism is often multi-drug resistant (MDR), can persist in the environment and forms a biofilm on environmental surfaces and wounds. This thesis describes research that investigates the role of the two component system AdeRS, which regulates production of the AdeABC MDR efflux pump. Its role in MDR, biofilm formation and virulence of A. baumannii was determined in mutants constructed for this study. Deletion of AdeRS or AdeABC resulted in increased susceptibility to antibiotics, decreased biofilm formation on biotic and abiotic surfaces and decreased virulence in a strain dependent manner. RNA-Seq revealed that loss of AdeRS or AdeB significantly altered the transcriptome, resulting in changed expression of many genes, notably those associated with antimicrobial resistance and virulence interactions. Thjs study demonstrated the scope of AdeRS mediated regulation and suggests that inhibition of AdeABC could prevent biofilm formation or colonisation in patients by A. baumannii and so provides a good target for drug discovery. This study also highlighted the differences between A. baumannii strains and shows that conclusions for the species should not be drawn from the study of single strains. |
