Regulation Of CzcCBA Gene Cluster Encoding A RND Pump And The Function Of PA4489 In Pseudomonas Aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen. It can cause seriously acute and chronic infections in human beings, and it is the third leading pathogen in nosocomial infections. P. aeruginosa has high intrinsic multidrug resistance to many antimicrobial drugs. Investigation of antibiotic resistance mechanisms and virulence factors in P. aeruginosa is critical for understanding its pathogenesis and controlling its infection. One of the resistance mechanisms known is the efflux of antibiotics by RND pumps. Previous studies in our laboratory indicate that the gene cluster czcCBA, encoding one of the 12 known and putative RND pumps in P. aeruginosa, is induced by Zn²⁺. In this study the regulation of the czcCBA gene cluster has been investigated by transposon mutagensis. After screening about 20000 mutant clones, 7 mutants were identified that affected the expression of czcCBA. An putativeα-2M gene (PA4489) in P. aeruginosa identified by bioinformatics analysis has also been investigated. An isogenic marker-freeα-2M deletion mutant of P. aeruginosa PAO1 was constructed and its survival ability in the presence of polymixin was compared with that of the wild type strain. It was found that yfa-α₂M mutant exhibited lower resistance to polymixin, indicating this gene may attribute to the resistance of P. aeruginosa against antibiotics.