Genomic microdiversity of Mycobacterium africanum in Sénégal

INTRODUCTION: Mycobacterium africanum is responsible for up to half of tuberculosis cases in West Africa and comprises four sub lineages. Its genomic diversity remains undescribed in Sénégal where M. africanum was first described and where the present study was conducted. RESULTS: Whole Genome Sequencing (WGS) identified one M. africanum lineage L5 isolate and 50 M. africanum lineage L6 isolates, with a predominance of sub lineage L6.1.1 (24/50, 43.7%) across seven of eight regions of Sénégal. The Dakar region gathered all the sub lineages (L5.3, L6.1, L6.1.1, L6.1.3, L6.2.3, L6.3.1, L6.3.2, L6.3.3, unclassified L6), except for sub lineage L6.2. Further Single Nucleotide Polymorphisms (SNPs) analysis revealed substantial genetic diversity among the lineage L6 isolates with mean value of 668.54 (±239.61), while themedian was 465 SNPs (interquartile range = 400, median absolute deviation:163.09). According to the World health Organization Catalogue of mutations in the Mycobacterium tuberculosis complex and their association with drug resistance, WGS predicted antibiotic resistance in 16 strains. Comparing Drug Susceptibility Testing (DST) and WGS results showed complete concordance across 19 DST tested strains. CONCLUSION: This study highlights the diversity of M. africanum in Sénégal, with intra-lineage genomic variability and predicted antimicrobial resistance. The presence of synonymous mutations in the absence of resistance-associated variants suggests that WGS-based predictions of drug resistance should be interpreted with caution.