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Open Access Research article

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

Fred S Sarfo12*, Richard O Phillips12, Jihui Zhang3, Mohammed K Abass4, Justice Abotsi4, Yaw A Amoako1, Yaw Adu-Sarkodie12, Clive Robinson3 and Mark H Wansbrough-Jones3

Author Affiliations

1 Komfo Anokye Teaching Hospital, Kumasi, Ghana

2 School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

3 St. George’s University of London, London, UK

4 Agogo Presbyterian Government Hospital, Ministry of Health, Agogo, Ghana

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BMC Infectious Diseases 2014, 14:202  doi:10.1186/1471-2334-14-202

Published: 15 April 2014

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.

Keywords:
Mycobacterium ulcerans; Mycolactone; Biomarker; Antibiotic therapy; Prognosis; Treatment response