Insight into the genetic diversity of Mycobacterium bovis isolated from cattle in Ghana

Bovine tuberculosis (bTB), caused primarily by Mycobacterium bovis, poses significant risks to cattle and public health in Ghana. Previous studies reported varying prevalence (3%-21%) and M. bovis strain distributions, necessitating a deeper understanding of the molecular epidemiology of bTB to guide control strategies. This study investigated the genetic diversity and phylogenetic relationships of M. bovis isolates from cattle in Ghanaian abattoirs and compared results with strains from other African countries. Spoligotyping analysis of 28 M. bovis isolates confirmed 6 distinct spoligotypes, with SB0944 being the most prevalent (64.3%). Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) genotyping analysis further resolved the isolates into 22 genotypes, with loci MIRU26, QUB26, and ETR-A showing the highest allelic diversity. Mixed infections were found in 10% of culture-confirmed cases, indicating a high risk of co-infection with multiple strains in the area. Comparative analysis revealed that Ghanaian isolates clustered within the African 1 (Af1) clonal complex, consistent with strains from Nigeria, Burkina Faso, and Cameroon, but distinct from the BCG-like and other strains that were dominant in Algeria and, to some extent, in Mali. Minimal strain homogenization of West-Central Africa with other regions suggests localized evolution, shaped by ecological barriers, regulated transhumance, and possible competitive exclusion among strains. These findings provide evidence for the need for region-specific bTB control measures that reflect Africa's unique livestock dynamics and micro-epidemic patterns. Enhanced surveillance with advanced genotyping methods could improve outbreak tracking and inform targeted interventions to mitigate bTB's impact on livestock in this region.IMPORTANCEBovine tuberculosis (bTB), caused primarily by Mycobacterium bovis, is a neglected disease in many low- and middle-income countries, including Ghana. Our study reveals that while M. bovis strains in Ghana show high local genetic diversity, they belong almost exclusively to a single clonal complex (Af1) shared across West-Central Africa. Despite regional regulations governing transhumance and cattle movement, the observed strain mixing suggests an "island-like" evolutionary structure for M. bovis in this area; that is, diverse within West-Central African countries but genetically isolated. This pattern is shaped by natural barriers, such as deserts and forests, which restrict strain flow while permitting intense intra-regional transmission. Understanding M. bovis evolution in this context is essential for tailoring effective, region-specific interventions. Our findings highlight the need to treat West-Central Africa as a community of interconnected but genetically distinct bTB zones, calling for both local action and coordinated regional strategies to mitigate bTB.