title: Chlamydia Serine Protease Inhibitor, targeting HtrA, as a New Treatment for Koala Chlamydia infection.
abstract: 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 vitro and 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 significant 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.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, 4059, Australia.
authors.forename: Amba
authors.initials: A
authors.lastname: Lawrence
authors.affiliation: Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydoore, QLD, 4558, Australia.
authors.forename: Tamieka
authors.initials: T
authors.lastname: Fraser
authors.affiliation: Australia Zoo Wildlife Hospital, Beerwah, QLD, 4519, Australia.
authors.forename: Amber
authors.initials: A
authors.lastname: Gillett
authors.affiliation: New Zealand's National School of Pharmacy, University of Otago, Dunedin 9054 New Zealand.
authors.forename: Joel D A
authors.initials: JD
authors.lastname: Tyndall
authors.affiliation: Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydoore, QLD, 4558, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Timms
authors.affiliation: Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydoore, QLD, 4558, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Polkinghorne
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, 4059, Australia.|School of Life Sciences, University of Technology Sydney, Broadway, NSW, 2007, Australia.
authors.forename: Wilhelmina M
authors.initials: WM
authors.lastname: Huston
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D023521:Chlamydophila Infections / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary; D016993:Chlamydophila pneumoniae / Q000201:enzymology*; D048368:Phascolarctidae / Q000382:microbiology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases