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Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease

BACKGROUND: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique fe...

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Autores principales: Sarfo, Fred S, Phillips, Richard O, Zhang, Jihui, Abass, Mohammed K, Abotsi, Justice, Amoako, Yaw A, Adu-Sarkodie, Yaw, Robinson, Clive, Wansbrough-Jones, Mark H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021496/
https://www.ncbi.nlm.nih.gov/pubmed/24731247
http://dx.doi.org/10.1186/1471-2334-14-202
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author Sarfo, Fred S
Phillips, Richard O
Zhang, Jihui
Abass, Mohammed K
Abotsi, Justice
Amoako, Yaw A
Adu-Sarkodie, Yaw
Robinson, Clive
Wansbrough-Jones, Mark H
author_facet Sarfo, Fred S
Phillips, Richard O
Zhang, Jihui
Abass, Mohammed K
Abotsi, Justice
Amoako, Yaw A
Adu-Sarkodie, Yaw
Robinson, Clive
Wansbrough-Jones, Mark H
author_sort Sarfo, Fred S
collection PubMed
description BACKGROUND: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical and bacteriological response to therapy. METHODS: Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy. RESULTS: Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were detected in a proportion of these slowly healing lesions during and after treatment. CONCLUSIONS: Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in optimising antibiotic therapy.
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spelling pubmed-40214962014-05-16 Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease Sarfo, Fred S Phillips, Richard O Zhang, Jihui Abass, Mohammed K Abotsi, Justice Amoako, Yaw A Adu-Sarkodie, Yaw Robinson, Clive Wansbrough-Jones, Mark H BMC Infect Dis Research Article BACKGROUND: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical and bacteriological response to therapy. METHODS: Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy. RESULTS: Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were detected in a proportion of these slowly healing lesions during and after treatment. CONCLUSIONS: Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in optimising antibiotic therapy. BioMed Central 2014-04-15 /pmc/articles/PMC4021496/ /pubmed/24731247 http://dx.doi.org/10.1186/1471-2334-14-202 Text en Copyright © 2014 Sarfo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sarfo, Fred S
Phillips, Richard O
Zhang, Jihui
Abass, Mohammed K
Abotsi, Justice
Amoako, Yaw A
Adu-Sarkodie, Yaw
Robinson, Clive
Wansbrough-Jones, Mark H
Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease
title Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease
title_full Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease
title_fullStr Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease
title_full_unstemmed Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease
title_short Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease
title_sort kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for mycobacterium ulcerans disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021496/
https://www.ncbi.nlm.nih.gov/pubmed/24731247
http://dx.doi.org/10.1186/1471-2334-14-202
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