Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis

Gloeckl, Sarina, Ong, Vanissa A., Patel, Pooja, Tyndall, Joel D. A., Timms, Peter, Beagley, Kenneth W., Allan, John A., Armitage, Charles W., Turnbull, Lynne, Whitchurch, Cynthia B., Merdanovic, Melisa, Ehrmann, Michael, Powers, James C., Oleksyszyn, Jozef, Verdoes, Martijn, Bogyo, Matthew and Huston, Wilhelmina M. 2013. Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis. Molecular Microbiology 89 (4) , pp. 676-689. 10.1111/mmi.12306

Full text not available from this repository.

Abstract

The mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease for this organism. Identification and application of a unique CtHtrA inhibitor (JO146) to cultures of Chlamydia resulted in a complete loss of viable elementary body formation. JO146 treatment during the replicative phase of development resulted in a loss of Chlamydia cell morphology, diminishing inclusion size, and ultimate loss of inclusions from the host cells. This completely prevented the formation of viable Chlamydia elementary bodies. In addition to its effect on the human Chlamydia trachomatis strain, JO146 inhibited the viability of the mouse strain, Chlamydia muridarum, both in vitro and in vivo. Thus, we report a chemical biology approach to establish an essential role for Chlamydia CtHtrA. The function of CtHtrA for Chlamydia appears to be essential for maintenance of cell morphology during replicative the phase and these findings provide proof of concept that proteases can be targeted for antimicrobial therapy for intracellular pathogens.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QP Physiology
Publisher: Wiley-Blackwell
ISSN: 0950-382X
Last Modified: 04 Jun 2017 06:10
URI: http://orca.cf.ac.uk/id/eprint/56918

Citation Data

Cited 5 times in Google Scholar. View in Google Scholar

Cited 29 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item