HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit Article Swipe
Natalie Strange
,
Laurence Don Wai Luu
,
Vanissa A. Ong
,
Bryan A. Wee
,
Matthew J. A. Phillips
,
Laura C. McCaughey
,
Joel R. Steele
,
Christopher K. Barlow
,
Charles G. Cranfield
,
Garry S. A. Myers
,
Rami Mazraani
,
Charles O. Rock
,
Peter Timms
,
Wilhelmina M. Huston
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1128/jb.00371-23
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1128/jb.00371-23
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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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1128/jb.00371-23
- OA Status
- green
- Cited By
- 1
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4392510258
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4392510258Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1128/jb.00371-23Digital Object Identifier
- Title
-
HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exitWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-03-06Full publication date if available
- Authors
-
Natalie Strange, Laurence Don Wai Luu, Vanissa A. Ong, Bryan A. Wee, Matthew J. A. Phillips, Laura C. McCaughey, Joel R. Steele, Christopher K. Barlow, Charles G. Cranfield, Garry S. A. Myers, Rami Mazraani, Charles O. Rock, Peter Timms, Wilhelmina M. HustonList of authors in order
- Landing page
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https://doi.org/10.1128/jb.00371-23Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/11025325Direct OA link when available
- Concepts
-
Biology, Chlamydia trachomatis, Intracellular, Cerulenin, Intracellular parasite, Protease, Microbiology, Chlamydiae, Biochemistry, Fatty acid, Cell biology, Enzyme, Virology, Fatty acid synthaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2024: 1Per-year citation counts (last 5 years)
- References (count)
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51Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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