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HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit.
Strange, Natalie; Luu, Laurence; Ong, Vanissa; Wee, Bryan A; Phillips, Matthew J A; McCaughey, Laura; Steele, Joel R; Barlow, Christopher K; Cranfield, Charles G; Myers, Garry; Mazraani, Rami; Rock, Charles; Timms, Peter; Huston, Wilhelmina M.
Afiliación
  • 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.
  • Phillips MJA; The Roslin Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
  • McCaughey L; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
  • Steele JR; Australian Institute for Microbiology and Infection, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
  • Barlow CK; School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
  • Cranfield CG; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
  • Myers G; Department of Biochemistry and Molecular Biology, Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Mazraani R; Department of Biochemistry and Molecular Biology, Monash Proteomics and Metabolomics Platform, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Rock C; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
  • Timms P; Australian Institute for Microbiology and Infection, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
  • Huston WM; School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
J Bacteriol ; 206(4): e0037123, 2024 04 18.
Article en En | MEDLINE | ID: mdl-38445896
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Chlamydia trachomatis / Ácidos Grasos Idioma: En Revista: J Bacteriol Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Chlamydia trachomatis / Ácidos Grasos Idioma: En Revista: J Bacteriol Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos