WSU / UI - Genetic regulation of developmental transitions in Chlamydia Bacteria of the genus Chlamydia include the significant human pathogens C. trachomatis, a leading cause of sexually transmitted infections, and C. pneumonia, a cause of significant respiratory disease. All chlamydiae are obligate intracellular parasites that depend on infection of a host cell to undergo a bi-phasic developmental cycle. Following host cell invasion by the infectious Elementary Body (EB), transition to the replicative but non- infectious Reticulate Body (RB) is essential for propagation. Differentiation of the RB back to the EB is essential to generate infectious progeny. The EB form has historically been regarded as metabolically inert. However, recent data suggest that EBs can respond to specific molecular signals, including glucose 6- phosphate and ATP that are predicted to be present at mucosal surfaces. The ability of EBs to respond to specific nutrients is consistent with their ability to respond actively to cues in their environment even before internalization into a host cell. Via analysis of EB pre-invasion molecular events (e.g., transcription, and maintenance of infectivity over time) and mathematical modeling, this project is aimed at determining the role of active EB metabolic responses during initial interactions with mucosal surfaces, and identification of gene regulatory events that control chlamydial morphological differentiation.

Public Health Relevance

WSU / UI - Genetic regulation of developmental transitions in Chlamydia ! Bacteria of the genus Chlamydia cause serious infections including sexually transmitted diseases and the potentially blinding ocular infection trachoma. All chlamydiae depend on transition between an infectious Elementary Body (EB) form and a replicative Reticulate Body (RB) form. This project aims to determine the extent to which the EB form is metabolically active during interaction with mucosal surfaces, and model and identify physiologically relevant factors (e.g., genetic regulatory elements) influencing chlamydial differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI130072-02
Application #
9746576
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Vincent, Leah Rebecca
Project Start
2018-07-17
Project End
2022-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Washington State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Grieshaber, Scott; Grieshaber, Nicole; Yang, Hong et al. (2018) Impact of Active Metabolism on Chlamydia trachomatis Elementary Body Transcript Profile and Infectivity. J Bacteriol 200: