We aim to learn how Chlamydia trachomatis secreted effectors direct cellular changes both individually and cooperatively within fruit flies (Drosophila melanogaster). Our preliminary data indicate that expression of chlamydial Tarp in flies leads to both macroscopic (curled bristles) and microscopic (irregular microvilli) developmental defects. The fruit fly model organism contains well defined polarized cells and developmental programs which can be quantitatively evaluated. This level of precision in a polarized cell model allows for the molecular dissection of individual C. trachomatis effectors and assessment of effector cooperation which has not yet been investigated. Known targets of the early C. trachomatis effectors such as actin, Crk adapters, Src tyrosine kinases, and PI3K are conserved in the fruit fly model suggesting cellular changes observed in flies are likely to mimic the effects on human tissues. In the short term, we believe that the fruit fly model will provide mechanistic insight into chlamydial effector directed host pathogen interactions and in the long term may serve as a powerful platform to explore bacterial genes of unknown function. 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.

Public Health Relevance

The sexually transmitted disease causing bacteria, Chlamydia trachomatis, uses a small collection of bacterial secreted proteins to infect human tissues. The goal of this research proposal is to elucidate the function of these proteins and to examine whether these bacterial proteins cooperate to drive the host cellular changes needed to initiate an infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI148999-02
Application #
10115601
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Vincent, Leah Rebecca
Project Start
2020-03-01
Project End
2022-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Central Florida
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
150805653
City
Orlando
State
FL
Country
United States
Zip Code
32826