Koala cathelicidin PhciCath5 has antimicrobial activity, including against Chlamydia pecorum.
Emma Peel, Yuanyuan Cheng, Julianne T Djordjevic, Denis O'Meally, Mark Thomas, Michael Kuhn, Tania C Sorrell, Wilhelmina M Huston, Katherine Belov
Author Information
Emma Peel: School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Yuanyuan Cheng: School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Julianne T Djordjevic: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia. ORCID
Denis O'Meally: Center for Gene Therapy, Beckman Research Institute of the City of Hope, Duarte, California, United States of America.
Mark Thomas: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.
Michael Kuhn: Zoetis, Veterinary Medicine Research and Development, Kalamazoo, Michigan, United States of America.
Tania C Sorrell: Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
Wilhelmina M Huston: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.
Katherine Belov: School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia. ORCID
Devastating fires in Australia over 2019-20 decimated native fauna and flora, including koalas. The resulting population bottleneck, combined with significant loss of habitat, increases the vulnerability of remaining koala populations to threats which include disease. Chlamydia is one disease which causes significant morbidity and mortality in koalas. The predominant pathogenic species, Chlamydia pecorum, causes severe ocular, urogenital and reproductive tract disease. In marsupials, including the koala, gene expansions of an antimicrobial peptide family known as cathelicidins have enabled protection of immunologically naïve pouch young during early development. We propose that koala cathelicidins are active against Chlamydia and other bacteria and fungi. Here we describe ten koala cathelicidins, five of which contained full length coding sequences that were widely expressed in tissues throughout the body. Focusing on these five, we investigate their antimicrobial activity against two koala C. pecorum isolates from distinct serovars; MarsBar and IPTaLE, as well as other bacteria and fungi. One cathelicidin, PhciCath5, inactivated C. pecorum IPTaLE and MarsBar elementary bodies and significantly reduced the number of inclusions compared to the control (p<0.0001). Despite evidence of cathelicidin expression within tissues known to be infected by Chlamydia, natural PhciCath5 concentrations may be inadequate in vivo to prevent or control C. pecorum infections in koalas. PhciCath5 also displayed antimicrobial activity against fungi and Gram negative and positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Electrostatic interactions likely drive PhciCath5 adherence to the pathogen cell membrane, followed by membrane permeabilisation leading to cell death. Activity against E. coli was reduced in the presence of 10% serum and 20% whole blood. Future modification of the PhciCath5 peptide to enhance activity, including in the presence of serum/blood, may provide a novel solution to Chlamydia infection in koalas and other species.
