HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit.

Autor:	Strange N; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia., Luu L; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia., Ong V; Faculty of Health, Queensland University of Technology, Kelvin Grove, Queensland, Australia., Wee BA; Faculty of Health, Queensland University of Technology, Kelvin Grove, Queensland, Australia.; The Roslin Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom., Phillips MJA; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia., McCaughey L; Australian Institute for Microbiology and Infection, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.; School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom., Steele JR; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.; Department of Biochemistry and Molecular Biology, Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Barlow CK; Department of Biochemistry and Molecular Biology, Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Cranfield CG; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia., Myers G; Australian Institute for Microbiology and Infection, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia., Mazraani R; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia., Rock C; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Timms P; Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, Queensland, Australia., Huston WM; Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	Journal of bacteriology [J Bacteriol] 2024 Apr 18; Vol. 206 (4), pp. e0037123. Date of Electronic Publication: 2024 Mar 06.
DOI:	10.1128/jb.00371-23
Abstrakt:	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. Importance: Chlamydia trachomatis is an important obligate intracellular pathogen that has a unique biphasic developmental cycle. HtrA is an essential stress or virulence protease in many bacteria, with many different functions. Previously, we demonstrated that HtrA is critical for Chlamydia using a novel inhibitor. In the present study, we characterized genetic variants of Chlamydia trachomatis with reduced susceptibility to the HtrA inhibitor. The variants were changed in membrane fatty acid composition, outer membrane proteins, and transcription of stress genes. Earlier and more synchronous cellular exit was observed. Combined, this links stress response to fatty acids, membrane proteins, and HtrA interplay with the outcome of disrupted timing of chlamydial cellular exit. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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