+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The Serine Protease Pic From Enteroaggregative Escherichia coli Mediates Immune Evasion by the Direct Cleavage of Complement Proteins

The Serine Protease Pic From Enteroaggregative Escherichia coli Mediates Immune Evasion by the Direct Cleavage of Complement Proteins

Journal of Infectious Diseases 212(1): 106-115

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 DH5α 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 α' 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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 059031633

Download citation: RISBibTeXText

PMID: 25583166

DOI: 10.1093/infdis/jiv013

Related references

The serine protease motif of EspC from enteropathogenic Escherichia coli produces epithelial damage by a mechanism different from that of Pet toxin from enteroaggregative E. coli. Infection and Immunity 72(6): 3609-3621, 2004

Cytoskeletal effects induced by pet, the serine protease enterotoxin of enteroaggregative Escherichia coli. Infection and Immunity 67(5): 2184-2192, 1999

Distribution of serine protease autotransporters of Enterobacteriaceae in typical and atypical enteroaggregative Escherichia coli. Infection Genetics and Evolution 50: 83-86, 2017

Pet serine protease from enteroaggregative Escherichia coli stimulates the inflammatory response activating human macrophages. Bmc Microbiology 16(1): 158, 2016

Short report: high prevalence of serine protease autotransporter cytotoxins among strains of enteroaggregative Escherichia coli. American Journal of Tropical Medicine and Hygiene 80(2): 294-301, 2009

Pet the serine protease from enteroaggregative Escherichia coli induce cytoskeleton alterations of epithelial cells associated with fodrin disruption. Abstracts of the General Meeting of the American Society for Microbiology 100: 104, 2000

EspP, a serine protease of enterohemorrhagic Escherichia coli, impairs complement activation by cleaving complement factors C3/C3b and C5. Infection and Immunity 78(10): 4294-4301, 2010

The major pilin subunit of the AAF/II fimbriae from enteroaggregative Escherichia coli mediates binding to extracellular matrix proteins. Infection and Immunity 76(10): 4378-4384, 2008

Evidence for multiple modes of neutrophil serine protease recognition by the EAP family of Staphylococcal innate immune evasion proteins. Protein Science 27(2): 509-522, 2018

A single malaria merozoite serine protease mediates shedding of multiple surface proteins by juxtamembrane cleavage. Journal of Biological Chemistry 278(26): 23890-8, 2003

Residues in a conserved α-helical segment are required for cleavage but not secretion of an Escherichia coli serine protease autotransporter passenger domain. Journal of Bacteriology 193(15): 3748-3756, 2011

Residues in a Conserved alpha-Helical Segment Are Required for Cleavage but Not Secretion of an Escherichia coli Serine Protease Autotransporter Passenger Domain. 2011

Cleavage of the third component of complement (C3) by mannose-binding protein-associated serine protease (MASP) with subsequent complement activation. Immunobiology 194(4-5): 443-448, 1995

Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion. Immunobiology 221(5): 679-689, 2016

The Trypanosoma cruzi protease cruzain mediates immune evasion. Plos Pathogens 7(9): E1002139, 2011