Distinct mechanisms of integrin binding by Yersinia pseudotuberculosis adhesins determine the phagocytic response of host macrophages.

摘要: Summary The enteropathogenic yersiniae express two outer membrane adhesins, invasin and YadA, that contribute to pathogenesis. While binds directly β1 integrin receptors with high affinity, YadA indirectly through extracellular matrix (ECM) components. In this study, Yersinia pseudotuberculosis inv yadA mutants were used investigate how these distinct binding mechanisms compare potentially compete in activating signalling pathways promoting bacterial uptake by host macrophages. The efficiency of adhesin-mediated phagocytic responses was found be dependent on the relative expression surface as well ECM proteins milieu. Under conditions low concentrations ECM, dominant adhesin, levels phagocytosis coincident robust sustained activation protein tyrosine kinases Fak Pyk2, phosphorylation adaptor molecule Cas small GTPase Rac1. presence higher became functional adhesin its ability engage via an bridge. We propose a model whereby promotes prolonged cascades inducing ‘high-affinity’ conformation clustering. postulate YadA–ECM more transient arises from clustering context cross-linked fibrillar network.