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

Samuel Phillips, Bonnie L. Quigley, Ammar Aziz, Wendy Bergen, Rosemary Booth, Michael Pyne, Peter Timms

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Abstract

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.

Original languageEnglish
Article numbere0221109
Pages (from-to)1-16
Number of pages16
JournalPLoS One
Volume14
Issue number8
DOIs
Publication statusPublished - 15 Aug 2019

Fingerprint

Phascolarctidae
cystitis
Chlamydia
Cystitis
Genes
antibiotics
transcriptomics
Oxygen
Anti-Bacterial Agents
oxygen
genes
Innate Immunity
Phascolarctos cinereus
therapeutics
Chemokine Receptors
Therapeutics
bladder
reactive oxygen species
Reactive Oxygen Species
Vaccines

Cite this

Phillips, Samuel ; Quigley, Bonnie L. ; Aziz, Ammar ; Bergen, Wendy ; Booth, Rosemary ; Pyne, Michael ; Timms, Peter. / Antibiotic treatment of Chlamydia-induced cystitis in the koala is linked to expression of key inflammatory genes in reactive oxygen pathways. In: PLoS One. 2019 ; Vol. 14, No. 8. pp. 1-16.
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abstract = "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.",
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Antibiotic treatment of Chlamydia-induced cystitis in the koala is linked to expression of key inflammatory genes in reactive oxygen pathways. / Phillips, Samuel; Quigley, Bonnie L.; Aziz, Ammar; Bergen, Wendy; Booth, Rosemary; Pyne, Michael; Timms, Peter.

In: PLoS One, Vol. 14, No. 8, e0221109, 15.08.2019, p. 1-16.

Research output: Contribution to journalArticleResearchpeer-review

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