Chlamydia trachomatis highjacks host MYO1C for actin cage recruitment at the bacterial inclusion.

Chlamydia trachomatis (Ct), a Gram-negative obligate intracellular pathogen, manipulates host actin dynamics to facilitate its entry, development, and exit. It assembles a dynamic actin cage around its intracellular niche, known as the 'inclusion', which provides structural stability for bacterial growth, and is crucial for exit via the non-cell-lytic extrusion process. We found that Ct recruits Myosin 1 C (MYO1C), a ubiquitous actin dependent motor protein, to the inclusion throughout its life cycle. Consequently, loss of MYO1C activity reduced Ct infection and the production of bacterial progenies. Mechanistically, MYO1C functions as a dynamic tether that assembles an actin cage around the inclusion membrane, as depletion of MYO1C or its inhibition by pentachloropseudilin (PClP) leads to the loss of the actin network surrounding the inclusion. In vitro reconstitution assays revealed that the presence of purified MYO1C was necessary and sufficient to build an actin cage around giant membranous vesicles. In summary, our findings identified MYO1C as a novel host target of Ct and provided mechanistic evidence for its role as a dynamic tether to recruit the essential actin cage around the bacterial inclusion.