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


Autoria(s): 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.
Data(s)

2015

Resumo

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.

Formato

application/pdf

Identificador

http://eprints.qut.edu.au/88050/

Publicador

BioMed Central

Relação

http://eprints.qut.edu.au/88050/1/12866_2015_Article_533.pdf

DOI:10.1186/s12866-015-0533-2

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).

http://purl.org/au-research/grants/NHMRC/553020

Direitos

Copyright 2015 2015 Marsh et al.

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.

Fonte

School of Biomedical Sciences; School of Chemistry, Physics & Mechanical Engineering; Faculty of Health; Institute of Health and Biomedical Innovation; Science & Engineering Faculty

Palavras-Chave #Chlamydia #HtrA #Genetics #Heat Shock #Intracellular
Tipo

Journal Article