Molecular determinants of virulence in drug-resistant ‘Mycobacterium tuberculosis’ (DR-MTB) strains circulating in Ethiopia: implications for transmission and treatment

PhD Candidate: Asmare Mekonnen
Institution: Addis Ababa University, School of Biomedicine and Medical Laboratory Sciences
Supervisors: Prof. Balako Gumi; Dr Kelemework Adane; Dr Ketema Tafesse; Dr Yared Merid; Dr Abyot Meaza

This PhD project investigates why some drug-resistant tuberculosis (DR-TB) strains cause more severe disease and spread more effectively than others. Tuberculosis remains a major public health challenge in Ethiopia, particularly in its drug-resistant forms, which are more difficult and costly to treat. While the genetic mutations responsible for drug resistance are well known, much less is understood about how these mutations interact with broader genomic variation to influence bacterial virulence and disease severity.

The study aims to identify key molecular determinants that drive virulence in DR-TB strains circulating in Ethiopia. Using a cross-sectional design, clinical isolates will be collected from multiple tuberculosis reference laboratories across the country. Advanced genomic techniques, including whole genome sequencing and spoligotyping, will be used to analyse genetic variation, lineage distribution, and resistance profiles. These data will be linked to clinical information to explore associations between bacterial genetics, disease severity, and transmission patterns.

The project is expected to generate a comprehensive map of highly virulent DR-TB strains in Ethiopia and identify genetic markers associated with increased pathogenicity. By improving understanding of how virulence and drug resistance interact, the findings may support the development of more targeted diagnostics, inform treatment strategies, and guide public health interventions.