PMID:25583166

Citation	'Abreu, AG, Fraga, TR, Martínez, AP, Kondo, MY, Juliano, MA, Juliano, L, Navarro-Garcia, F, Isaac, L, Barbosa, AS and Elias, WP (2015) The serine protease Pic from enteroaggregative Escherichia coli mediates immune evasion by the direct cleavage of complement proteins. J. Infect. Dis. '
Abstract	Enteroaggregative and uropathogenic E. 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 three pathways. Pic cleaves purified C3/C3b and other proteins from the classical 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 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.
Links	PubMed Online version:10.1093/infdis/jiv013
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ECO44:PIC		GO:0045916: negative regulation of complement activation	ECO:0000314:		P		Figure 1 shows that Pic inhibits all three complement cascades, as shown by the decrease in deposition of C4b with anti-C4 antibodies. Figure 2 shows that Pic cleaves complement proteins. Figure 3 shows that Pic present in the supernatant of E.coli is also able to cleave purified complement proteins. Figure 4 shows that it cleaves complement proteins found in human serum	complete CACAO 10542

References

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