Sarfo, FS; Phillips, RO; Zhang, J; Abass, MK; Abotsi, J; Amoako, YA; Adu-Sarkodie, Y; Robinson, C; Wansbrough-Jones, MH
(2014)
Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease.
BMC Infectious Diseases, 14 (202).
ISSN 1471-2334
https://doi.org/10.1186/1471-2334-14-202
SGUL Authors: Robinson, Clive Wansbrough-Jones, Mark Harding Phillips, Richard
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Abstract
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.
Item Type: |
Article
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Additional Information: |
© 2014 Sarfo et al.; licensee BioMed Central Ltd. 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. |
Keywords: |
Adolescent, Adult, Aged, Animals, Anti-Bacterial Agents, Buruli Ulcer, Child, Child, Preschool, Female, Humans, Macrolides, Male, Mass Spectrometry, Mice, Middle Aged, Subcutaneous Tissue, Skin, Tissue Distribution, Young Adult, Mycobacterium ulcerans, Mycolactone, Biomarker, Antibiotic therapy, Prognosis, Treatment response, Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, BURULI ULCER, HOST IMMUNE-RESPONSE, CYTOKINE PRODUCTION, TOXIN, STREPTOMYCIN, MACROLIDE, COMBINATION, EFFICACY, RIFAMPIN, GROWTH, Microbiology, 0605 Microbiology, 1103 Clinical Sciences, 1108 Medical Microbiology |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
BMC Infectious Diseases |
ISSN: |
1471-2334 |
Language: |
eng |
Dates: |
Date | Event |
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15 April 2014 | Published |
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PubMed ID: |
24731247 |
Web of Science ID: |
WOS:000335474200002 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/107235 |
Publisher's version: |
https://doi.org/10.1186/1471-2334-14-202 |
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