| Full text | |
| Author(s): |
Abreu, Afonso G.
[1]
;
Fraga, Tatiana R.
[2]
;
Granados Martinez, Adriana P.
[2]
;
Kondo, Marcia Y.
[3]
;
Juliano, Maria A.
[3]
;
Juliano, Luiz
[3]
;
Navarro-Garcia, Fernando
[4]
;
Isaac, Lourdes
[2]
;
Barbosa, Angela S.
[1]
;
Elias, Waldir P.
[1]
Total Authors: 10
|
| Affiliation: | [1] Univ Sao Paulo, Butantan Inst, Bacteriol Lab, BR-05508 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil
[4] Inst Politecn Nacl CINVESTAV, Ctr Invest & Estudios Avanzados, Dept Cell Biol, Mexico City, DF - Mexico
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Journal of Infectious Diseases; v. 212, n. 1, p. 106-115, JUL 1 2015. |
| Web of Science Citations: | 16 |
| 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 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. (AU) | |
| FAPESP's process: | 12/50191-4 - Synthesis, kinetic studies and applications of substrates and inhibitors for proteolytic enzymes |
| Grantee: | Maria Aparecida Juliano |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 11/14103-0 - Biological activities of the autotransporter protein PIC of atypical enteropathogenic Escherichia coli |
| Grantee: | Waldir Pereira Elias Junior |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 10/50043-0 - Complement system and pathogenicity of Leptospires: mechanisms of activation and evasion, identification of bacterial ligands, characterization of proteases and establishment of an in vivo murine model |
| Grantee: | Lourdes Isaac |
| Support Opportunities: | Research Projects - Thematic Grants |