YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis

Abstract

The PTPase YopH of Yersinia is essential to the ability of these bacteria to block phagocytosis. Wild-type Yersinia pseudotuberculosis, but not the yopH mutant strain, resisted phagocytosis by J774 cells. Ingestion of a yopH mutant was dependent on tyrosine kinase activity. Transcomplementation with wild-type yopH restored the anti-phagocytic effect, whereas introduction of the gene encoding the catalytically inactive yopHC403A was without effect. The PTPase inhibitor orthovanadate impaired the anti-phagocytic effect of the wild-type strain, further demonstrating the importance of bacteria-derived PTPase activity for this event. The ability to resist phagocytosis indicates that the effect of the bacterium is immediately exerted when it becomes associated with the phagocyte. Within 30 s after the onset of infection, wild-type Y. pseudotuberculosis caused a YopH-dependent dephosphorylation of phosphotyrosine proteins in J774 cells. Furthermore, interaction of the cells with phagocytosable strains led to a rapid and transient increase in tyrosine phosphorylation of paxillin and some other proteins, an event dependent on the presence of the bacterial surface-located protein invasin. Co-infection with the phagocytosable strain and the wild-type strain abolished the induction of tyrosine phosphorylation. Taken together, the present findings demonstrate an immediate YopH-mediated dephosphorylation of macrophage phosphotyrosine proteins, suggesting that this PTPase acts by preventing early phagocytosis-linked signalling in the phagocyte.

Involvement of focal adhesion kinase in invasin-mediated uptake

“…Engagement of ␤1 integrins by invasin may lead to the recruitment and activation of pp125FAK and src-family kinases, followed by phosphorylation of signaling intermediates that are associated with actin rearrangements such as paxillin and p130CAS. In support of this model, phosphorylation of paxillin has been observed upon cellular challenge with bacteria expressing invasin (30), an event considered to be downstream of FAK action (27,29).…”

Real-time imaging of type III secretion: Salmonella SipA injection into host cells

“…This study presents a real-time visualization of the type III secretion process and explains why S. typhimurium can trigger host cell responses within 1 min after docking (29)(30)(31). However, the amounts and kinetics of effector protein delivery did vary somewhat between individual bacteria.…”

Paxillin: Adapting to Change

“…TGF-␤ and activin A, which stimulate receptor serine/threonine kinase activity, also indirectly trigger paxillin tyrosine phosphorylation (212). Similarly, agonists of many 7-pass transmembrane serpentine family receptors induce paxillin tyrosine phosphorylation including acetylcholine (298), epineph- (3,288) and exposure to their toxins including Pasteurella multocida toxin, cytotoxic necrotizing factor 1, dermonecrotic toxin, and lipopolysaccharide (136,137) can also induce paxillin tyrosine phosphorylation. In each of these scenarios, profound alterations in the cytoskeleton are effected that are essential to activate and regulate host defenses.…”