Journal article
HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit
Journal of Bacteriology, Vol.206(4), pp.1-21
2024
PMID: 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.IMPORTANCEChlamydia 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.
Details
- Title
- HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit
- Authors
- Natalie Strange - University of Technology SydneyLaurence Luu - University of Technology SydneyVanissa Ong - Queensland University of TechnologyBryan A. Wee - Queensland University of TechnologyMatthew J. A. Phillips - University of Technology SydneyLaura McCaughey - University of Technology SydneyJoel R. Steele - University of Technology SydneyChristopher K. Barlow - Monash UniversityCharles G. Cranfield - University of Technology SydneyGarry Myers - University of Technology SydneyRami Mazraani - University of Technology SydneyCharles Rock - St. Jude Children's Research HospitalPeter Timms - University of the Sunshine Coast, Queensland, Centre for BioinnovationWilhelmina M. Huston (Corresponding Author) - University of Technology Sydney
- Publication details
- Journal of Bacteriology, Vol.206(4), pp.1-21
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/jb.00371-23
- ISSN
- 1098-5530
- PMID
- 38445896
- Data Availability
- Sequence and expression data is available at EBA Project Accession number PRJEB12312 and the corresponding project in the Genbank's Sequence Read Archive.
- Organisation Unit
- Centre for Bioinnovation; School of Science, Technology and Engineering
- Language
- English
- Record Identifier
- 991010098902621
- Output Type
- Journal article
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- Domestic collaboration
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- Microbiology
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