The Roles Of PA2800 In Antibiotic Resistance And Virulence In Pseudomonas Aeruginosa

Pseudomonas aeruginosa is a Gram-negative pathogen that is widespread in the environment and has high potential to cause human infection. It is one of the leading infectious agents in hospitals. With widespbread usage of antimicrobial drugs including algriculture use, multi-drug resistance in P. aeruginosa has become a more and more serious problem in clinical therapy. It is critically important to investigate drug resistance mechanisms in P. aeruginosa in order to control its infections.In the previous research in our lab, several transponson mutants including PA2800 mutant were found be more sensitive to antibiotic than the wild type. PA2800 belongs to the class four genes and its function is currently unknown. In this study the function of this gene and the mechanism of its involvement in antibiotic resistance were invetsigated.A PA2800 knockout mutant, PAO1 (APA2800) was constructed and drug susciptibility in LB solid and liquid was compared between wild type PAO1 and the mutant PAO1(â–³PA2800). The result showed that the mutant had elevated susceptibility to tetracycline, ciprofloxacin and chloramphenico. The expression of PA2800 was also found increased by two or three times in the presence of sub-inhibitory tetracycline and erythromycin concentration. This indicates that the PA2800 gene is related to durg resistance in P. aeruginosa. The virulence of the mutant was also compared with PAO1, the death rate of Drosophila injected with the mutant was higherr than that injected witrh wild type PAO1, indicating increased virulence in the mutant. Moreover, the expression of virulence factor genes rhlR and znuA was enhanced to different levels in the mutant PAO1(â–³PA2800). The increased virulence factors might be the reason of the higher killing rate of the PA2800 mutant. The increased virulence was not related to molotily or biofilm production as both phenotypes remained unchanged in the mutant. OprH is an outer membrane protein, it can lead to increased susceptibility to chloramphenicol and quinolones if overexpressed. The expression of oprH was elevated in the PA2800 mutant, probably one of the reasons that higher susceptibility to ciprofloxacin and chloramphenico was observed in PA2800 mutant.