Chlamydia trachomatis represents a significant health concern world-wide. A substantial burden exists due to the prevalence and the combined health and socioeconomic impact of acute and chronic disease. All Chlamydia species express a type III secretion system (T3SS), and this mechanism likely contributes significantly to overall pathogenesis. Chlamydiae are obligate intracellular parasites that undergo a complex developmental cycle, and this biology has historically impeded rapid progress in understanding pathogenesis. The newly acquired ability to inactivate chlamydial genes via insertion or deletion mutagenesis has greatly facilitated characterization of virulence factors. Unfortunately, significant barriers remain in the application of genetics in elucidating molecular mechanisms of virulence. For example, there is currently no mechanism to generate null strains for gene products that are absolutely essential for chlamydial propagation in cell culture. To this end, we have adapted the fluorescence-reported allelic exchange mutagenesis technique to facilitate creation of conditional null strains in essential genes. Preliminary data describing such a situation for a type III effector gene are presented herein. We propose to validate and further develop our approach while revealing the function of a highly important effector protein. At the end of these studies, we will have established new approaches that will benefit the entire Chlamydia research community and advance the understanding of how T3S manifests during chlamydial infection.

Public Health Relevance

Chlamydia trachomatis, an agent of sexually transmitted disease, relies on a specialized secretion mechanism to deploy proteins exerting anti-host activities essential to pathogenesis. This proposal contains work designed to use mutagenesis of specific genes that are essential for chlamydial survival to determine their specific contributions to chlamydial disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI144648-01
Application #
9722542
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Vincent, Leah Rebecca
Project Start
2019-02-11
Project End
2021-01-31
Budget Start
2019-02-11
Budget End
2020-01-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40526