Microbiome and Resistome of Mycobacterium ulcerans lesions

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Buruli ulcer (BU) is a neglected bacterial disease, predominantly occurring in West Africa. The causative agent Mycobacterium ulcerans induces severe ulcerative skin lesions mainly in young children. The treatment of choice is an antibiotic combination therapy of rifampicin and clarithromycin supported by surgical debridement. Treatment success depends on several factors comprising the size of the affected skin, the composition of the bacterial wound flora, and also treatment compliance. However, despite successes of antibiotic therapy, a significant proportion of patients do not respond adequately to treatment, and wound healing varies substantially. In a considerable number of cases, therapy is delayed or has failed completely. Except from possible poor patient compliance, the bacterial composition of BU lesions might be a driving factor affecting the healing process, as well as antimicrobial resistance of bacteria within the wounds including those of M. ulcerans. These factors have so far received little attention in endemic areas in the most affected countries. Therefore, this project aims to analyse the wound microbiome of BU lesions by culture-based methods in addition to next generation sequencing analysis (NGS), where metagenomic analyses will complement the investigations to uncover the full range of bacterial diversity. BU patients will be enrolled in seven hospitals of Kumasi, Ghana, and surrounding cities. Samples will be collected from patients up to 9 months if the wounds do not heal. The proposed study will allow identification of relevant bacteria involved in the development of BU lesion, and their healing processes. NGS screens may also identify bacteria that cannot be cultured by standard methods, and have previously not been associated with delayed wound healing. In addition, sequencing based antibiotic resistance tests will be supported by phenotypic resistance screens. The bacterial composition of BU wounds will be compared amongst patients where despite adequate antibiotic therapy poor healing of the lesions was observed, and those that responded well to therapy. Individuals with a long and poor healing history are at risk to be colonized by a peculiar microbial flora and/or carrying antibiotic resistant bacteria including M. ulcerans strains. Thus, preparedness for the emergence of resistant bacteria is necessary to respond adequately to changing therapy regimes.