Journal article

In vitro susceptibility of recent Chlamydia trachomatis clinical isolates to the CtHtrA inhibitor JO146

Vanissa A Ong, Amba Lawrence, Peter Timms, Lenka A Vodstrcil, Sepehr N Tabrizi, Kenneth W Beagley, John A Allan, Jane S Hocking, Wilhelmina M Huston

Microbes and Infection | ELSEVIER | Published : 2015

Abstract

The present study aimed to establish if a previously identified Chlamydia trachomatis HtrA (CtHtrA) inhibitor, JO146, is effective against currently circulating clinical isolates to validate if CtHtrA is a clinically relevant target for future therapeutic development. Inhibition of CtHtrA during the middle of the chlamydial replicative cycle until the completion of the cycle resulted in loss of infectious progeny for six unique clinical isolates representing different serovars. This supports the potential for CtHtrA to be a clinically relevant target for development of new therapeutics and suggests the importance of further investigation of JO146 as a lead compound.

Grants

Awarded by NHMRC Project


Awarded by ARC Linkage Project from The Wesley and Saint Andrews Research Institute


Funding Acknowledgements

The project that collected the clinical isolates that were used in this study was funded by NHMRC Project Grant (APP1023239). The work conducted here to analyse the impact of JO146 on these clinical isolates was funded by ARC Linkage Project LP1102500077 which includes partner funding from The Wesley and Saint Andrews Research Institute. Professor Matt Bogyo (Stanford University) and Dr Joel Tyndall (University of Otago) contributed to the identification of JO146. We wish to thank the ACTS study nurses Ruthy McIver and Karen Worthington, and also acknowledge Marcus Chen, Christopher K Fairley and Anna McNulty for facilitating recruitment in their clinics.