title: Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds.
abstract: The obligate intracellular bacterial pathogen Chlamydia trachomatis replicates within a large vacuole or "inclusion" that expands as bacteria multiply but is maintained as an intact organelle. Here, we report that the inclusion is encased in a scaffold of host cytoskeletal structures made up of a network of F-actin and intermediate filaments (IF) that act cooperatively to stabilize the pathogen-containing vacuole. Formation of F-actin at the inclusion was dependent on RhoA, and its disruption led to the disassembly of IFs, loss of inclusion integrity, and leakage of inclusion contents into the host cytoplasm. In addition, IF proteins were processed by the secreted chlamydial protease CPAF to form filamentous structures at the inclusion surface with altered structural properties. We propose that Chlamydia has co-opted the function of F-actin and IFs to stabilize the inclusion with a dynamic, structural scaffold while minimizing the exposure of inclusion contents to cytoplasmic innate immune-surveillance pathways.
authors.affiliation: Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Yadunanda
authors.initials: Y
authors.lastname: Kumar
authors.forename: Raphael H
authors.initials: RH
authors.lastname: Valdivia
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000201:enzymology / Q000502:physiology*; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000382:microbiology; D007382:Intermediate Filaments / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D010447:Peptide Hydrolases; D020742:rhoA GTP-Binding Protein