| Autor: |
McCullough A; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA., Jabeena CA; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA., Steiert B; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.; Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA., Faris R; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA., Weber MM; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA. |
| Abstrakt: |
Chlamydia trachomatis ( C.t. ) is the causative agent of several human diseases, including the sexually transmitted infection chlamydia and eye infection trachoma. As an obligate intracellular bacterial pathogen, invasion is essential for establishing infection and subsequent pathogenesis. To facilitate invasion, C.t. secretes effector proteins through its type III secretion system (T3SS). These effectors facilitate bacterial entry by manipulating multiple pathways involved in host actin cytoskeletal regulation. Previous studies have demonstrated that the T3SS effector protein TmeA is crucial for C.t. invasion, as it recruits and activates N-WASP. This interaction leads to recruitment and activation of the Arp2/3 complex, promoting cytoskeletal rearrangements at the invasion site to facilitate C.t. uptake. In this study, we define the role of the N-WASP CRIB domain in mediating this interaction, showing that TmeA acts as a functional mimic of Cdc42 in activating N-WASP. Additionally, we identified TOCA-1 as another host protein that directly interacts with TmeA. In other bacterial pathogens, notably Enterohemorrhagic E. coli , N-WASP and TOCA-1 are hijacked to mediate pedestal formation. Using siRNA to knockdown N-WASP and TOCA-1, followed by transmission electron microscopic, we observed that both N-WASP and TOCA-1 are important for in C.t. -mediated pedestal formation. Collectively, these findings reveal a unique mechanism of TmeA-mediated invasion, where direct interactions with N-WASP and TOCA-1 facilitate pedestal formation. |
