title: The Serine Protease Pic From Enteroaggregative Escherichia coli Mediates Immune Evasion by the Direct Cleavage of Complement Proteins.
abstract: 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.
authors.affiliation: Laboratory of Bacteriology, Butantan Institute.
authors.forename: Afonso G
authors.initials: AG
authors.lastname: Abreu
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo.
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: Fraga
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo.
authors.forename: Adriana P
authors.initials: AP
authors.lastname: Granados Martínez
authors.affiliation: Department of Biophysics, Federal University of São Paulo, Brazil.
authors.forename: Marcia Y
authors.initials: MY
authors.lastname: Kondo
authors.affiliation: Department of Biophysics, Federal University of São Paulo, Brazil.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.affiliation: Department of Biophysics, Federal University of São Paulo, Brazil.
authors.forename: Luiz
authors.initials: L
authors.lastname: Juliano
authors.affiliation: Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Navarro-Garcia
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
authors.affiliation: Laboratory of Bacteriology, Butantan Institute.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Barbosa
authors.affiliation: Laboratory of Bacteriology, Butantan Institute.
authors.forename: Waldir P
authors.initials: WP
authors.lastname: Elias
mesh_terms: D003165:Complement System Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D057131:Immune Evasion; D012697:Serine Endopeptidases / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D037521:Virulence Factors; D003165:Complement System Proteins; C541114:Pic protein, E coli; D012697:Serine Endopeptidases
keywords: Escherichia coli; Pic; complement system; immune evasion; serine protease