Original Contribution to the Taxonomy and Pathogenicity Mechanisms of Neglected Actinomycetes Causing Madura Foot in North West Nigerian Communities

Madura foot (mycetoma) caused by filamentous actinomycetes, particularly Nocardia and Streptomyces species, is a neglected tropical disease inflicting chronic disability in communities of northern Nigeria, yet the taxonomic identity and pathogenicity mechanisms of causative actinomycetes in North West Nigerian cases have not been rigorously characterised. This dissertation makes an original taxonomic and mechanistic contribution to the understanding of actinomycetes causing Madura foot in North West Nigerian communities, focusing on Sokoto and Kebbi States. Clinical specimens including mycetoma granules and tissue biopsies were collected from 80 patients attending treatment centres. Actinomycetes were isolated under selective conditions and characterised by polyphasic taxonomy combining 16S rRNA gene sequencing, DNA-DNA hybridisation, chemotaxonomic analysis, and MALDI-TOF MS profiling. Pathogenicity mechanisms were investigated by proteomic analysis of secreted virulence factors, biofilm forming capacity, and macrophage survival assays using THP-1 cells. Taxonomic investigation identified six phylospecies of causative actinomycetes, including two candidate novel species with 16S rRNA gene similarity below 97 percent to any described species. Virulence proteomics identified unique caseinolytic protease and siderophore biosynthesis enzyme signatures in North West Nigerian strains compared to reference isolates. Macrophage survival assays confirmed intracellular persistence mediated by inhibition of phagosome-lysosome fusion. The dissertation makes original taxonomic discoveries and pathogenicity mechanism contributions of global significance for mycetoma research and treatment targeting. Keywords: Madura foot, mycetoma, actinomycetes, taxonomy, pathogenicity mechanisms