PMID:26945067

Citation	'Agrahari, G, Liang, Z, Glinton, K, Lee, SW, Ploplis, VA and Castellino, FJ (2016) Streptococcus pyogenes employs strain-dependent mechanisms of C3b inactivation to inhibit phagocytosis and killing of bacteria. J. Biol. Chem. '
Abstract	Evasion of complement-mediated opsonophagocytosis enables Group A Streptococcus pyogenes (GAS) to establish infection. Different strain-dependent mechanisms are employed by the host to accomplish this goal. In general, GAS inhibits the amplification of the complement cascade on its cell surface by facilitating the degradation of C3b, an opsonin, to an inactive product, iC3b, in a step catalyzed by Factor I (FI) and its cofactor, Factor H (FH), with or without participation of human host plasmin (hPm). GAS recruits FH to its cell surface via FH receptors, which are transcriptionally controlled by the two-component cluster of virulence responder-sensor (CovRS) system. The manner in which FI/FH and hPm function together on GAS cells is unknown. Using GAS strain AP53, which strongly binds host human plasminogen/plasmin (hPg/hPm) directly via a hPg/hPm surface receptor (PAM), we show that both FI/FH and hPm sequentially cleave C3b. While FI/FH proteolytically cleaves C3b into iC3b, PAM-bound hPm catalyzes cleavage of iC3b into multiple smaller peptides. Unlike AP53, GAS strain M23ND weakly binds FH, and recruits hPg/hPm to its cell surface indirectly via fibrinogen bound to M-protein, M23. In this case, FH/FI cleaves C3b into iC3b, with negligible degradation of iC3b by hPm that is bound to fibrinogen on the cells. AP53 and M23ND display similar resistance to human neutrophil-mediated phagocytosis, which results in a corresponding high lethality in mice after injection of these cells. These results suggest that GAS utilizes diverse mechanisms degrade C3b and thus to protect bacterial cells from the complement response of the host.
Links	PubMed Online version:10.1074/jbc.M115.704221
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
STRP1:CAS9	Contributes to	GO:0050765: negative regulation of phagocytosis	ECO:0000315:		P		Streptococcus pyogenes uses Factor H to degrade C3B which is responsible for opsinization. This results in evading phagocytosis.	complete CACAO 11363
STRPY:D4QE70		GO:0050765: negative regulation of phagocytosis	ECO:0000315:		P		In Figure 3, the experiment shows that C3b is cleaved by the F1/FH complex which inhibits opsonization that is needed to induce phagocytosis.	complete CACAO 11706
STRPY:PAM	Contributes to	GO:0050765: negative regulation of phagocytosis	ECO:0000315:		P		Figure 2	complete CACAO 11532

References

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