Chlamydia Serine Protease Inhibitor, targeting HtrA, as a New Treatment for Koala Chlamydia infection
Amba Lawrence1, Tamieka Fraser2, Amber Gillett3, Joel D. A. Tyndall4, Peter Timms2, Adam Polkinghorne2 & Wilhelmina M. Huston1,5
1Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, 4059, Australia.
2Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydoore, QLD, 4558, Australia.
3Australia Zoo Wildlife Hospital, Beerwah, QLD, 4519, Australia.
4New Zealand’s National School of Pharmacy, University of Otago, Dunedin, 9054 New Zealand. 5School of Life Sciences, University of Technology Sydney, Broadway, NSW, 2007, Australia.
Correspondence and requests for materials should be addressed to W.M.H. (email: )
The koala, an iconic marsupial native to Australia, is a threatened species in many parts of the country. One major factor in the decline is disease caused by infection with Chlamydia. Current therapeutic strategies to treat chlamydiosis in the koala are limited. This study examines the eﬀectiveness of an inhibitor, JO146, which targets the HtrA serine protease for treatment of C. pecorum and C. pneumoniae in vitroand ex vivo with the aim of developing a novel therapeutic for koala Chlamydia infections. Clinical isolates from koalas were examined for their susceptibility to JO146. In vitro studies demonstrated that treatment with JO146 during the mid-replicative phase of C. pecorum or C. pneumoniae infections resulted in a signifcant loss of infectious progeny. Ex vivo primary koala tissue cultures were used to demonstrate the efficacy of JO146 and the non-toxic nature of this compound on peripheral blood mononuclear cells and primary cell lines established from koala tissues collected at necropsy. Our results suggest that inhibition of the serine protease HtrA could be a novel treatment strategy for chlamydiosis in koalas.