Dynamin-dependent entry of Chlamydia trachomatis is sequentially regulated by the effectors TarP and TmeA

Chlamydia invasion of epithelial cells is a pathogen-driven process
involving two functionally distinct effectors – TarP and TmeA. They
collaborate to promote robust actin dynamics at sites of entry. Here, we
extend studies on the molecular mechanism of invasion by implicating the
host GTPase dynamin 2 (Dyn2) in the completion of pathogen uptake.
Importantly, Dyn2 function is modulated by TarP and TmeA at the levels of
recruitment and activation through oligomerization, respectively.
TarP-dependent recruitment requires phosphatidylinositol 3-kinase and the
small GTPase Rac1, while TmeA has a post-recruitment role related to Dyn2
oligomerization. This is based on the rescue of invasion duration and
efficiency in the absence of TmeA by the Dyn2 oligomer-stabilizing small
molecule activator Ryngo 1-23. Notably, Dyn2 also regulated the turnover
of TarP- and TmeA-associated actin networks, with disrupted Dyn2 function
resulting in aberrant turnover dynamics, thus establishing the
interdependent functional relationship between Dyn2 and the effectors TarP
and TmeA.