Tuesday, April 1, 2025
4/1/2025
Regulation of cytoskeletal reorganization by a single effector during Chlamydia infection - ABSTRACT Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted infections worldwide. Frequent reinfection due to the lack of protective immunity can result in considerable reproductive consequences such as pelvic inflammatory disease and infertility. Without a prophylactic vaccine, it is paramount to identify the intracellular survival strategies of C. trachomatis and how they impact pathology and disease progression. Thus, our long-term goal is to determine how interactions between Ct and its host contribute to virulence and result in pathological outcomes. Ct is an obligate intracellular bacterium that replicates within a parasitic niche called the inclusion. Ct hijacks various host pathways to weave actin and microtubule cytoskeletal scaffolds around the inclusion. Microtubule scaffolds then become post-translationally modified (PTM-MT), which is critical for positioning Golgi ministacks around the inclusion, allowing Ct easier access to lipids. In contrast, actin scaffolds form a physical barrier to prevent the premature lysis of the inclusion and the release of bacteria into the cytosol. Interestingly, Ct utilizes a single effector protein, InaC/CT813, to coordinate the formation of these functionally distinct scaffolds. However, how InaC directs the formation of each scaffold, as well as their role in vivo, remains unknown. Identifying the contributions of each cytoskeletal scaffold to Ct pathogenesis has been hampered by the inability to selectively inactivate the different scaffolds. To overcome this obstacle, we have generated a unique library of InaC mutants that are defective in either PTM-MT or actin scaffolds. Using our InaCmutant Ct library, we will test the hypothesis that distinct protein domains generate different cytoskeletal scaffolds, which are important for Ct development and pathogenesis in vivo. For the first time, we will be able to establish the importance of individual cytoskeletal scaffolds in Ct development and how they contribute to virulence both in vitro and in the animal model.
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