The First Phylogeographic Population Structure and Analysis of Transmission Dynamics of M. africanum West African 1— Combining Molecular Data from Benin, Nigeria and Sierra Leone

Abstract

Mycobacterium africanum is an important cause of tuberculosis (TB) in West Africa. So far, two lineages called M. africanum West African 1 (MAF1) and M. africanum West African 2 (MAF2) have been defined. Although several molecular studies on MAF2 have been conducted to date, little is known about MAF1. As MAF1 is mainly present in countries around the Gulf of Guinea we aimed to estimate its prevalence in Cotonou, the biggest city in Benin. Between 2005–06 we collected strains in Cotonou/Benin and genotyped them using spoligo- and 12-loci-MIRU-VNTR-typing. Analyzing 194 isolates, we found that 31% and 6% were MAF1 and MAF2, respectively. Therefore Benin is one of the countries with the highest prevalence (37%) of M. africanum in general and MAF1 in particular. Moreover, we combined our data from Benin with publicly available genotyping information from Nigeria and Sierra Leone, and determined the phylogeographic population structure and genotypic clustering of MAF1. Within the MAF1 lineage, we identified an unexpected great genetic variability with the presence of at least 10 sub-lineages. Interestingly, 8 out of 10 of the discovered sub-lineages not only clustered genetically but also geographically. Besides showing a remarkable local restriction to certain regions in Benin and Nigeria, the sub-lineages differed dramatically in their capacity to transmit within the human host population. While identifying Benin as one of the countries with the highest overall prevalence of M. africanum, this study also contains the first detailed description of the transmission dynamics and phylogenetic composition of the MAF1 lineage.

Unexpected Genomic and Phenotypic Diversity of Mycobacterium africanum Lineage 5 Affects Drug Resistance, Protein Secretion, and Immunogenicity

“…1968; Gehre, Otu et al 2013). Most notable are a relatively slow growth, dependence on pyruvate in liquid media and small colonies on solid media, which can lead to underdiagnosis in a clinical setting (Castets et al.…”

“…1968; Keating et al. 2005; Gehre, Otu et al 2013). Since early biochemical studies did not discern between different lineages of M. africanum (Castets et al.…”

“…2001; Brudey et al. 2004; Gehre, Antonio et al 2013). Of course, the resolution of spoligotyping is inferior to that of the whole genome sequencing applied here.…”

“…2016) and phenotypic traits of these strains that might affect their diagnosis, transmission, or virulence characteristics are rarely investigated (de Jong et al. 2010; Gehre, Otu et al 2013). M. africanum L5 strains are endemic in a number of countries around the Gulf of Guinea, such as Cameroon, Nigeria, Benin, Ghana, Ivory coast, and Sierra Leone, where they cause between 6% and 39% of all tuberculosis cases (de Jong et al.…”

Consequences of genomic diversity in Mycobacterium tuberculosis

“…Lineage 5 and Lineage 6 are also known as M. africanum West Africa 1 and West Africa 2, respectively, and almost exclusively occur in West Africa or in recent immigrants from those regions [71]. Lineage 6 occurs primarily in the Western part of West Africa, whereas Lineage 5 dominates further to the East in regions bordering the Gulf of Guinea [71,72]. Similarly, the recently discovered Lineage 7 is confined to Ethiopia and recent immigrants from that part of the world.…”