Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.

Chlamydiosis is the major infectious disease responsible for significant morbidity and mortality in free-living koalas. Recently, it was reported that 28.5% of koalas infected with chlamydiosis were presented with no overt clinical signs. Identification and quantification of changes in plasma biomar...

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Main Authors: Chien-Jung Chen, Benjamin Kimble, Astrid Van Aggelen, Shalini Fischer, Cheyne Flanagan, Amber Gillett, Jackie Reed, Jodie Wakeman, Merran Govendir
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0314945
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author Chien-Jung Chen
Benjamin Kimble
Astrid Van Aggelen
Shalini Fischer
Cheyne Flanagan
Amber Gillett
Jackie Reed
Jodie Wakeman
Merran Govendir
author_facet Chien-Jung Chen
Benjamin Kimble
Astrid Van Aggelen
Shalini Fischer
Cheyne Flanagan
Amber Gillett
Jackie Reed
Jodie Wakeman
Merran Govendir
author_sort Chien-Jung Chen
collection DOAJ
description Chlamydiosis is the major infectious disease responsible for significant morbidity and mortality in free-living koalas. Recently, it was reported that 28.5% of koalas infected with chlamydiosis were presented with no overt clinical signs. Identification and quantification of changes in plasma biomarkers' fluctuations have the potential to enhance C. pecorum detection and facilitate the monitoring of therapeutic efficacy of antibiotics to treat this disease in koalas. Therefore, concentrations of the essential amino acid tryptophan, tryptophan's metabolite kynurenine, and the kynurenine:tryptophan ratio were quantified by high-performance liquid chromatography in the plasma of clinically normal koalas (n = 35), koalas identified with chlamydial disease (n = 35) and koalas that had other non-chlamydial co-morbidities (n = 10). Results showed that there was a significant difference between the clinically normal versus diseased, and clinically normal versus 'other' (both p < 0.001) in kynurenine plasma concentrations and kynurenine:tryptophan ratio; and also between the clinically normal and diseased in tryptophan plasma concentrations (p = 0.001). Proposed reference ranges of tryptophan, kynurenine, and kynurenine:tryptophan ratio in koalas are: 4.27-10.4 μg/mL, 0.34-1.23 μg/mL, and 0.05-0.22, respectively. Proposed optimal cut-off points to differentiate between clinically normal and diseased are: ≤ 4.75 μg/mL (tryptophan), ≥ 0.88 μg/mL (kynurenine), and ≥ 0.12 (kynurenine:tryptophan); and ≤ 7.67 μg/mL (tryptophan), ≥ 1.18 μg/mL (kynurenine), and ≥ 0.16 (kynurenine:tryptophan) to differentiate between released/recovered and euthanised of the diseased/'other' koalas. Significant differences in haematological and biochemical analytes were in the plasma globulins between the clinically normal and diseased koalas (p = 0.01), and in alkaline phosphatase between the clinically normal and 'other' koalas (p = 0.03). Although these potential biomarkers, especially tryptophan, may not be specific for detecting C. pecorum from the rest of the population, kynurenine and the kynurenine:tryptophan ratio may have a role in identifying unhealthy koalas from the clinically normal ones, irrespective of the underlying cause.
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spelling doaj-art-8b232ca3a066476f90188bf7e8846e1c2025-01-08T05:32:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031494510.1371/journal.pone.0314945Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.Chien-Jung ChenBenjamin KimbleAstrid Van AggelenShalini FischerCheyne FlanaganAmber GillettJackie ReedJodie WakemanMerran GovendirChlamydiosis is the major infectious disease responsible for significant morbidity and mortality in free-living koalas. Recently, it was reported that 28.5% of koalas infected with chlamydiosis were presented with no overt clinical signs. Identification and quantification of changes in plasma biomarkers' fluctuations have the potential to enhance C. pecorum detection and facilitate the monitoring of therapeutic efficacy of antibiotics to treat this disease in koalas. Therefore, concentrations of the essential amino acid tryptophan, tryptophan's metabolite kynurenine, and the kynurenine:tryptophan ratio were quantified by high-performance liquid chromatography in the plasma of clinically normal koalas (n = 35), koalas identified with chlamydial disease (n = 35) and koalas that had other non-chlamydial co-morbidities (n = 10). Results showed that there was a significant difference between the clinically normal versus diseased, and clinically normal versus 'other' (both p < 0.001) in kynurenine plasma concentrations and kynurenine:tryptophan ratio; and also between the clinically normal and diseased in tryptophan plasma concentrations (p = 0.001). Proposed reference ranges of tryptophan, kynurenine, and kynurenine:tryptophan ratio in koalas are: 4.27-10.4 μg/mL, 0.34-1.23 μg/mL, and 0.05-0.22, respectively. Proposed optimal cut-off points to differentiate between clinically normal and diseased are: ≤ 4.75 μg/mL (tryptophan), ≥ 0.88 μg/mL (kynurenine), and ≥ 0.12 (kynurenine:tryptophan); and ≤ 7.67 μg/mL (tryptophan), ≥ 1.18 μg/mL (kynurenine), and ≥ 0.16 (kynurenine:tryptophan) to differentiate between released/recovered and euthanised of the diseased/'other' koalas. Significant differences in haematological and biochemical analytes were in the plasma globulins between the clinically normal and diseased koalas (p = 0.01), and in alkaline phosphatase between the clinically normal and 'other' koalas (p = 0.03). Although these potential biomarkers, especially tryptophan, may not be specific for detecting C. pecorum from the rest of the population, kynurenine and the kynurenine:tryptophan ratio may have a role in identifying unhealthy koalas from the clinically normal ones, irrespective of the underlying cause.https://doi.org/10.1371/journal.pone.0314945
spellingShingle Chien-Jung Chen
Benjamin Kimble
Astrid Van Aggelen
Shalini Fischer
Cheyne Flanagan
Amber Gillett
Jackie Reed
Jodie Wakeman
Merran Govendir
Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.
PLoS ONE
title Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.
title_full Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.
title_fullStr Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.
title_full_unstemmed Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.
title_short Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas.
title_sort preliminary analyses of tryptophan kynurenine and the kynurenine tryptophan ratio in plasma as potential biomarkers for systemic chlamydial infections in koalas
url https://doi.org/10.1371/journal.pone.0314945
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