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

doi:10.1016/j.micinf.2015.09.004

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

Microbes Infect. 2015 Nov-Dec;17(11-12):738-44. doi: 10.1016/j.micinf.2015.09.004. Epub 2015 Sep 11.

Authors

Vanissa A Ong¹, Amba Lawrence¹, Peter Timms², Lenka A Vodstrcil³, Sepehr N Tabrizi⁴, Kenneth W Beagley¹, John A Allan⁵, Jane S Hocking⁶, Wilhelmina M Huston⁷

Affiliations

¹ School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Q Block, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia.
² School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Q Block, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia; Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, Australia.
³ Centre for Epidemiology and Biostatistics, Melbourne School of Population Health, University of Melbourne, Carlton, Australia; Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁴ Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, The Royal Women's Hospital, Australia.
⁵ Wesley and St Andrews Research Institute, The Wesley Hospital, Auchenflower, Australia; UC Health Clinical School, The Wesley Hospital, Auchenflower, Australia.
⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population Health, University of Melbourne, Carlton, Australia.
⁷ School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Q Block, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia; Wesley and St Andrews Research Institute, The Wesley Hospital, Auchenflower, Australia; School of Life Sciences, Faculty of Science, University of Technology, Sydney, Australia. Electronic address: Wilhelmina.Huston@uts.edu.au.

PMID: 26369711
DOI: 10.1016/j.micinf.2015.09.004

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.

Keywords: Chlamydia; Clinical isolate; HtrA; Inhibitor.

MeSH terms

Cell Line
Chlamydia trachomatis / drug effects*
Chlamydia trachomatis / isolation & purification*
Dipeptides / pharmacology*
Female
Humans
Organophosphonates / pharmacology*
Serine Endopeptidases / drug effects*
Serine Proteinase Inhibitors / pharmacology*

Substances

Dipeptides
JO146 compound
Organophosphonates
Serine Proteinase Inhibitors
Serine Endopeptidases