Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase production to be far less determinant of β-lactam resistance than previously indicated. The relative expression of the outer membrane porin channel, OprD, appears to have a much greater influence on phenotype. Both intrinsic efflux pump systems, MexAB-OprM and MexXY, proved necessary for resistance despite the degree of membrane impermeability. The induction of the acquired MexCD-OprJ and MexEF-OprN systems were found to considerably downregulate and impair the intrinsic efflux pump genes and proteins, respectively. Complex differential gene regulation that was phenotype dependent as well as highly correlated regulatory expression values continue to suggest higher ordered mechanisms yet to be understood. In addition, inhibitory overlap between the various resistance mechanisms supports the need for further expansion of gene targets as well as the modular response to treatment by P. aeruginosa. Further understanding could provide exploitation of regulatory feedback loops in which reversion of susceptibility towards intended agents may be achieved.
Date of publication
Dr. Ali Azghani, Dr. Brent Bill, Dr. Matthew Greenwold, Dr. Riqing Yu
Masters of Biology
Esmond, Dustin, "ASSESMENT OF ANTIBIOTIC RESISTANT GENE EXPRESSION IN CLINICAL ISOLATES OF PSEUDOMONAS AERUGINOSA" (2021). Biology Theses. Paper 68.
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