Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 212, Issue 1, Pages 106-115Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv013
Keywords
Pic; Escherichia coli; immune evasion; complement system; serine protease
Categories
Funding
- Sao Paulo Research Foundation - FAPESP [2011/14103-0, 2010/50043-0, 2012/50191-4]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [471340/2011-1, 470388/2010-2]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/50191-4] Funding Source: FAPESP
Ask authors/readers for more resources
Enteroaggregative and uropathogenic Escherichia coli, Shigella flexneri 2a, and the hybrid enteroaggregative/Shiga toxin-producing E. coli strain (O104:H4) are important pathogens responsible for intestinal and urinary tract infections, as well as sepsis and hemolytic uremic syndrome. They have in common the production of a serine protease called Pic. Several biological roles for Pic have been described, including protection of E. coli DH5a from complement-mediated killing. Hereby we showed that Pic significantly reduces complement activation by all 3 pathways. Pic cleaves purified C3/C3b and other proteins from the classic and lectin pathways, such as C4 and C2. Cleavage fragments of C3, C4, and C2 were also observed with HB101(pPic1) culture supernatants, and C3 cleavage sites were mapped by fluorescence resonance energy transfer peptides. Experiments using human serum as a source of complement proteins confirmed Pic proteolytic activity on these proteins. Furthermore, Pic works synergistically with the human complement regulators factor I and factor H, promoting inactivation of C3b. In the presence of both regulators, further degradation of C3 alpha' chain was observed. Therefore, Pic may contribute to immune evasion of E. coli and S. flexneri, favoring invasiveness and increasing the severity of the disorders caused by these pathogens.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available