Antibiotic treatment of Chlamydia-induced cystitis in the koala is linked to expression of key inflammatory genes in reactive oxygen pathways

• Published in: PloS one Vol. 14; no. 8; p. e0221109
• Main Authors: Phillips, Samuel, Quigley, Bonnie L, Aziz, Ammar, Bergen, Wendy, Booth, Rosemary, Pyne, Michael, Timms, Peter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.08.2019; Public Library of Science (PLoS)
• Subjects: Animals; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacterial infections; Biology and Life Sciences; Bladder; Causes of; Chemokines; Chlamydia; Chlamydia - metabolism; Chlamydia infections; Chlamydia Infections - drug therapy; Chlamydia Infections - metabolism; Chlamydia Infections - veterinary; Chlamydia pecorum; Complications; Complications and side effects; Criminal investigation; CYBB protein; Cystitis; Cystitis - drug therapy; Cystitis - metabolism; Cystitis - microbiology; Cystitis - veterinary; Cytokines; Death; Disease; Diseases; Dosage and administration; Down-regulation; Drug therapy; Education; Engineering; Gene expression; Gene Expression Regulation; Gene regulation; Genes; Genetic aspects; Genetic markers; Genomes; Health aspects; Hospitals; Immune clearance; Immune response; Immune system; Incontinence; Infections; Inflammation; Innate immunity; Irwin, Steve; Koalas; Markers; Medical treatment; Medicine and Health Sciences; Microbiology; Oxygen; Patient outcomes; Phascolarctidae - microbiology; Phascolarctos cinereus; Reactive oxygen species; Reactive Oxygen Species - metabolism; Regression analysis; Sexually transmitted diseases; Signal transduction; Signaling; STD; Urinary incontinence; Vaccination; Vaccines; Veterinary antibiotics; Wound healing; Zoos; Australia; Queensland Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221109

Chlamydial-induced cystitis in the koala (Phascolarctos cinereus) is currently treated by antibiotics. However, while reducing the chlamydial load, this treatment can also lead to gastrointestinal complications and death. Development of alternative treatments, such as a therapeutic chlamydial vaccine, are hindered by the lack of detailed understanding of the innate immune response to chlamydial clearance and disease regression during antibiotic treatment. Through clinical, microbiological and transcriptomic approaches, disease regression, bacterial clearance and innate immune responses were mapped in koalas with signs of chlamydial-induced cystitis while receiving anti-chlamydial antibiotics. Significant reduction in the signs of cystitis were observed during and post antibiotic treatment. This was observed as a thinning of the bladder wall and complete reversal of urinary incontinence. Transcriptomic analysis before treatment, at the end of treatment and prior to release identified significant down-regulation of specific genes involved in 21 biological pathways. Of these, the chemokine receptor signalling and NOD-like receptor signalling pathways where identified as important markers of inflammation. Specific genes within these pathways (NCF1 and NOX2) were significantly down-regulated, suggesting a decrease in reactive oxygen species production. Through the monitoring of specific clinical and transcriptomic markers, these findings allow detailed profiling of the clinical response to therapeutic vaccination in koalas with current signs of disease. This also adds to our understanding of innate immune responses to chlamydial infections and indicates that chlamydial-induced cystitis in the koala is linked to the regulation of reactive oxygen pathways.