The role of the bacterial protease Prc in the uropathogenesis of extraintestinal pathogenic Escherichia coli

Bibliographic Details
Title: The role of the bacterial protease Prc in the uropathogenesis of extraintestinal pathogenic Escherichia coli
Authors: Wen-Chun Huang, Chung-Yen Lin, Masayuki Hashimoto, Jiunn-Jong Wu, Ming-Cheng Wang, Wei-Hung Lin, Chang-Shi Chen, Ching-Hao Teng
Source: Journal of Biomedical Science, Vol 27, Iss 1, Pp 1-22 (2020)
Publisher Information: BMC, 2020.
Publication Year: 2020
Collection: LCC:Medicine
Subject Terms: Extraintestinal pathogenic Escherichia coli, Urinary tract infections, Protease Prc, Motility, Flagella, σE, Medicine
More Details: Abstract Background Extraintestinal pathogenic E. coli (ExPEC) remains one of the most prevalent bacterial pathogens that cause extraintestinal infections, including neonatal meningitis, septicemia, and urinary tract (UT) infections (UTIs). Antibiotic therapy has been the conventional treatment for such infections, but its efficacy has decreased due to the emergence of antibiotic-resistant bacteria. Identification and characterization of bacterial factors that contribute to the severity of infection would facilitate the development of novel therapeutic strategies. The ExPEC periplasmic protease Prc contributes to the pathogen’s ability to evade complement-mediated killing in the serum. Here, we further investigated the role of the Prc protease in ExPEC-induced UTIs and the underlying mechanism. Methods The uropathogenic role of Prc was determined in a mouse model of UTIs. Using global quantitative proteomic analyses, we revealed that the expression of FliC and other outer membrane-associated proteins was altered by Prc deficiency. Comparative transcriptome analyses identified that Prc deficiency affected expression of the flagellar regulon and genes that are regulated by five extracytoplasmic signaling systems. Results A mutant ExPEC with a prc deletion was attenuated in bladder and kidney colonization. Global quantitative proteomic analyses of the prc mutant and wild-type ExPEC strains revealed significantly reduced flagellum expression in the absence of Prc, consequently impairing bacterial motility. The prc deletion triggered downregulation of the flhDC operon encoding the master transcriptional regulator of flagellum biogenesis. Overexpressing flhDC restored the prc mutant’s motility and ability to colonize the UT, suggesting that the impaired motility is responsible for attenuated UT colonization of the mutant. Further comparative transcriptome analyses revealed that Prc deficiency activated the σE and RcsCDB signaling pathways. These pathways were responsible for the diminished flhDC expression. Finally, the activation of the RcsCDB system was attributed to the intracellular accumulation of a known Prc substrate Spr in the prc mutant. Spr is a peptidoglycan hydrolase and its accumulation destabilizes the bacterial envelope. Conclusions We demonstrated for the first time that Prc is essential for full ExPEC virulence in UTIs. Our results collectively support the idea that Prc is essential for bacterial envelope integrity, thus explaining how Prc deficiency results in an attenuated ExPEC.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1423-0127
Relation: https://doaj.org/toc/1423-0127
DOI: 10.1186/s12929-019-0605-y
Access URL: https://doaj.org/article/6b0cff1c2994467392c491e07d0cee1a
Accession Number: edsdoj.6b0cff1c2994467392c491e07d0cee1a
Database: Directory of Open Access Journals
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More Details
ISSN:14230127
DOI:10.1186/s12929-019-0605-y
Published in:Journal of Biomedical Science
Language:English