Jeanne Salje and her group based at CIMR have published two papers on Orientia tsutsugamushi, the bacterium that causes the vector-bourne human disease, scrub typhus. The first paper appears in PLOS Pathogens andis a collaboration with colleagues in Bangkok, Irvine and Oxford. It is an analysis of seven diverse strains of Orientia tsutsugamushi that reveals a multifaceted and complex interplay of virulence factors responsible for disease. The paper states:
“The data suggest that there is no single factor that predicts whether a strain will be pathogenic or not, but that disease in scrub typhus is a complex process resulting from the activity of multiple bacterial genes working together to drive different immune responses in the host, resulting in either clearance of the bacteria from the host, or escalating disease. Future work exploring the relationship of bacterial effector proteins will help to disentangle this complex relationship in mechanistic detail.”
The second article in Nature Communicationslooks at how Orientia tsutsugamushi relies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. It uncovers how the bacterium is coupled to the dynein machinery and how transport is regulated. It is written with colleagues in Bangkok and at the MRC Laboratory of Molecular Biology. The paper concludes:
“O. tsutsugamushi uses its autotransporter protein ScaC to recruit the dynein adaptors BICD1 and BICD2 for movement to the perinucleus. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD1 and BICD2 are required for efficient movement of O. tsutsugamushi during infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a role for BICD adaptors during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen.”