1. Reported events related to the replication cycle of Orientia tsutsugamushi in nonphagocytic cells.
Reported events related to the replication cycle of Orientia tsutsugamushi in nonphagocytic cells. Fibronectin in the ECM interacts with the Orientia antigen TSA56, and potentially with ScaC, for the attachment of bacteria to the host cell. This results in integrin-mediated signaling, involving FAK, Src, and Rho GTPase, with consequent actin cytoskeleton rearrangement, talin/paxillin recruitment, and clathrin-mediated endocytosis. The Orientia antigen ScaA and transmembrane syndecan-4 also mediate bacterial adhesion to nonphagocytic cells. At 1 hpi, Orientia colocalizes with early endosomal markers but at 2 hpi escapes from phagosomes through an unknown mechanism that requires compartment acidification and also evades cellular autophagy. It reaches the perinuclear region after moving through microtubules associated with the dynein-dynactin protein complex, where it replicates via binary fission. The secretion of effector cells participates as a virulence factor, probably via the T1SS and T4SS, disrupting the SCF1 ubiquitin ligase complex, degrading EF1α, and impairing protein translation. Also, Orientia colocalizes with the Golgi complex and moves backwards to the ER, producing membrane instability mediated by the effector protein Ank9. The release of Orientia particles occurs in a way similar to virus budding at 72 hpi and has been associated with lipid rafts and caveolin colocalization. MTOC, microtubule organizing center.
Fabián E. Díaz et al. Clin. Microbiol. Rev. 2018; doi: /CMR