Fatou Faal Poster 2024

Ms Fatou Faal

MRC The Gambia at LSHTM, Gambia

Investigating West Africa Circulating Mycobacterium tuberculosis Complex Lineages Response to Anti-Tuberculosis Treatment Approaches 

Poster Abstract

Tuberculosis is caused by Mycobacterium tuberculosis complex (MTBC) lineages. There are nine MTBC lineages worldwide, all found in Africa. Some lineages are distributed globally (L2 and 4), while others are restricted to specific geographical locations, M.africanum(L5 and6), mainly found in West Africa. Despite this diversity, drug-susceptible TB is treated with the same antibiotic combination for six months. MTBC lineages' genetic diversity has been shown to affect treatment response. Therefore, new-drugs accounting for this diversity are needed to control TB.
 
Total of 285 MTBC isolates from The Gambia with whole genome sequence data were used to identify important genetic mutations for structural bioinformatics analysis. Representative isolates of MTBC lineages were transformed using a reporter gene-tagged plasmid to confer luminescence and green fluorescence protein expression to bacilli. The direct effect of antibiotics was tested in the presence of the bacteria to determine the half-maximal inhibitory concentration 50(IC50) of each drug against the transformed MTBC lineage using the CDD-vault platform. The IC50 values were then aligned with the genetic variation in each lineage to derive an association.
 
The results revealed that some mutations within established drug resistant genes differed in MTBC lineages. The IC50 for rifampicin was 0.001-0.002, 0.003-0.004, 0.004, 0.007 and 0.008 for M. africanum L6, Mtb L2, M.bovis , Mtb L4 and M.africanum L5, respectively. M.africanum L6 had a lineage-specific mutation in the rpoB, but also fabG1 and gyrA/B genes. M.tuberculosisL4 had only a mutation in the katG gene, related to isoniazid resistance.
 
We have built a pipeline to integrate the genetic variation of MTBC isolates circulating in West Africa with phenotypic antibiotics’ susceptibility. This will be used to understand the molecular determinants of West African MTBC lineage responses to existing and new anti-TB drugs and host directed therapeutics. 

Biography

As a young scientist, I am deeply committed to catalyzing change in the realm of tuberculosis treatment. My aspiration is to play a pivotal role in the development of innovative treatment approaches for tuberculosis in Africa. This ambition has been profoundly influenced by my current role and the firsthand observation of the devastating toll of TB within my local community. I am convinced that I am positioned at the opportune moment to translate this vision into tangible outcomes through the acquisition of essential skills in my PhD project.