The role of protease Prc in pathogenesis of Extraintestinal Pathogenic Escherichia coli

Abstract

Extraintestinal Pathogenic Escherichia coli (ExPEC) are responsible for many extraintestinal infectious diseases such as neonatal meningitis bacteremia and urinary tract infections (UTIs) Antibiotic therapy is the traditional way to treat E coli infections However the rapid emergence of antibiotic resistant strains have become serious problems to manage the bacterial infections Therefore new antimicrobial strategies against the E coli-associated infections are urgently needed Bacterial factors required for the pathogens to cause infections will be potential targets for developing such strategies The periplasmic protease Prc may be a potential antimicrobial target for the development of new strategies against ExPEC infection because our laboratory has identified that Prc is required for ExPEC to cause bacteremia However it remains unclear whether this protease contributes to ExPEC infections in other host tissues In this study we revealed that deletion of prc decreased the ability of ExPEC to cause UTIs Based on the proteome analysis the major component of the flagellum filament FliC was down-regulated in the prc mutant Therefore the prc mutant of ExPEC showed defective motility which contributed to the decreased ability to colonize the bladder and kidney Deletion of prc triggered the activation of two extracytoplasmic signaling pathways the σE and the RcsCDB systems The activation of the systems downregulated the transcription of flhDC which encode the master regulator of flagellar biosynthesis and thus suppressed the expression of fliC In addition the lack of the Prc protease function was found be responsible for the defective motility of the prc mutant suggesting that the substrate of this protease may be involved in the defective phenotype of the mutant As expected accumulation of the known Prc substrate Spr in the prc mutant was shown to contribute to the activation of RcsCDB system and thus to suppress the bacterial motility This study strengthens an alternative role of Prc in the ExPEC UTIs other than the ExPEC bacteremia and substantiates the potential role of Prc as an antimicrobial targets

Date of Award	2016 Sept 1
Original language	English
Supervisor	Ching-Hao Teng (Supervisor)