The obligate intracellular bacterium Chlamydia trachomatis causes substantial morbidity in the US and worldwide. A C. trachomatis effector called Tarp for translocated actin recruiting protein is a candidate virulence factor. Tarp is tyrosine phosphorylated by a host cell kinase and is associated with actin recruitment during C. trachomatis entry. All reference and clinical isolates of Chlamydiae species examined to date harbor the tarP gene. We have identified and biochemically characterized four Tarp proteins domains including: i) a phosphorylation domain ii) a proline rich oligomerization domain iii) a G-actin binding and nucleating domain, and iv) two F-actin binding and bundling domains. We hypothesize that specific Tarp domains are required for bacterial entry and/or chlamydial development. We will test this hypothesis by: 1) analyzing C. trachomatis transformants that express Tarp domain deletion mutants and examine the ability of the mutant genes to function as dominant negative alleles thereby affecting invasion and development of the bacterial clones in host epithelial cells and 2) using a unique genetic strategy to target deletion of the chromosomal copy of the tarP gene in C. trachomatis transformants carrying a plasmid copy of wild type or mutant tarP. Elucidation of the molecular mechanisms employed by C. trachomatis to initiate a successful infection may provide clues that can be applied to novel therapeutic interventions for this prolific pathogen.
The sexually transmitted disease causing bacteria, Chlamydia trachomatis, infects an estimated 2.8 million people in the US annually. The goal of this research proposal is to employ new genetic approaches to examine the requirement for the C. trachomatis Tarp effector in chlamydial entry and developmental.
| Ghosh, Susmita; Park, Jinho; Thomas, Mitchell et al. (2018) Biophysical characterization of actin bundles generated by the Chlamydia trachomatis Tarp effector. Biochem Biophys Res Commun 500:423-428 |
| Parrett, Christopher J; Lenoci, Robert V; Nguyen, Brenda et al. (2016) Targeted Disruption of Chlamydia trachomatis Invasion by in Trans Expression of Dominant Negative Tarp Effectors. Front Cell Infect Microbiol 6:84 |
