Small molecule virulence factors and potential drugs from actinomycetoma organisms

Mycetoma is an orphan disease that is prevalent in sub-Saharan Africa and caused by fungi or actinobacteria. The disease is characterised by subcutaneous, tumour-like growths occurring predominantly on the lower limbs, which can then extend to bones and internal organs.
The main causative organisms of actinomycetoma are Actinomadura, Nocardia, or Streptomyces spp. Actinobacteria are Gram positive, filamentous organisms that make a very wide repertoire of small bioactive molecules including antibiotics, antifungals, anticancer agents, statins, etc. One of our aims is to understand the molecular basis of mycetoma and how the causative organisms elicit the disease. However, one very interesting facet of this disease is that the organisms appear to be able to combat innate and or adaptive immune effectors to establish long lived slow growing lesions. We assume that a key factor in the virulence of these organisms will lie in the synthesis of natural product bioactive molecules that interfere with specific immune mechanisms. Our partner organization, Demuris Ltd, has years of experience of mining actinomycetes for NPs with anti-infective properties - potential antibacterial or antifungal molecules. This project could enable them to diversify into another therapeutic area - immunomodulators. Immune dysfunction is a common problem in ageing patients. Therefore, this programme could, in the longer term, provide new interventions of significant use in the treatment of elderly patients or more generally patients with autoimmune disease, transplantation, and cancer treatment.