A Chlamydia trachomatis strain with a chemically generated amino acid substitution (P370L) in the cthtrA gene shows reduced elementary body production

Marsh, James W., Wee, Bryan A., Tyndall, Joel D.A., Lott, William B., Bastidas, Robert J., Caldwell, Harlan D., Valdivia, Raphael H., Kari, L., & Huston, Wilhelmina M. (2015) A Chlamydia trachomatis strain with a chemically generated amino acid substitution (P370L) in the cthtrA gene shows reduced elementary body production. BMC Microbiology, 15(194).

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Abstract

Background

Chlamydia (C.) trachomatis is the most prevalent bacterial sexually transmitted infection worldwide and the leading cause of preventable blindness. Genetic approaches to investigate C. trachomatis have been only recently developed due to the organism’s intracellular developmental cycle. HtrA is a critical stress response serine protease and chaperone for many bacteria and in C. trachomatis has been previously shown to be important for heat stress and the replicative phase of development using a chemical inhibitor of the CtHtrA activity. In this study, chemically-induced SNVs in the cthtrA gene that resulted in amino acid substitutions (A240V, G475E, and P370L) were identified and characterized.

Methods

SNVs were initially biochemically characterized in vitro using recombinant protein techniques to confirm a functional impact on proteolysis. The C. trachomatis strains containing the SNVs with marked reductions in proteolysis were investigated in cell culture to identify phenotypes that could be linked to CtHtrA function.

Results

The strain harboring the SNV with the most marked impact on proteolysis (cthtrAP370L) was detected to have a significant reduction in the production of infectious elementary bodies.

Conclusions

This provides genetic evidence that CtHtrA is critical for the C. trachomatis developmental cycle.

Impact and interest:

1 citations in Scopus
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ID Code: 88050
Item Type: Journal Article
Refereed: Yes
Keywords: Chlamydia, HtrA, Genetics, Heat Shock, Intracellular
DOI: 10.1186/s12866-015-0533-2
ISSN: 1471-2180
Divisions: Current > Schools > School of Biomedical Sciences
Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Funding:
Copyright Owner: Copyright 2015 2015 Marsh et al.
Copyright Statement: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Deposited On: 07 Oct 2015 00:33
Last Modified: 07 Oct 2015 22:26

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