Oral Presentation BacPath 2024

HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit (#7)

Laurence Don Wai Luu 1 , Natalie Strange 1 , Vanissa Ong 2 , Bryan Aidan A Wee 2 , Matthew J Phillips 1 , Laura McCaughey 3 , Joel R Steele 1 , Christopher K Barlow 4 , Charles G Cranfield 1 , Garry Myers 3 , Rami Mazraani 1 , Charles Rock 5 , Wilhelmina M Huston 6
  1. School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia
  2. Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia
  3. Australian Institute for Microbiology and Infection, University of Technology Sydney, Ultimo, NSW, Australia
  4. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  5. Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
  6. Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia

Chlamydia trachomatis is an intracellular bacterial pathogen that undergoes a biphasic developmental cycle, consisting of intracellular reticulate bodies and extracellular infectious elementary bodies. A conserved bacterial protease, HtrA, was shown previously to be essential for Chlamydia during the reticulate body phase, using a novel inhibitor (JO146). In this study, isolates selected for the survival of JO146 treatment were found to have polymorphisms in the acyl-acyl carrier protein synthetase gene (aasC). AasC encodes the enzyme responsible for activating fatty acids from the host cell or synthesis to be incorporated into lipid bilayers. The isolates had distinct lipidomes with varied fatty acid compositions. A reduction in the lipid compositions that HtrA prefers to bind to was detected, yet HtrA and MOMP (a key outer membrane protein) were present at higher levels in the variants. Reduced progeny production and an earlier cellular exit were observed. Transcriptome analysis identified that multiple genes were downregulated in the variants especially stress and DNA processing factors. Here, we have shown that the fatty acid composition of chlamydial lipids, HtrA, and membrane proteins interplay and, when disrupted, impact chlamydial stress response that could trigger early cellular exit.