Tuberculosis caused by Mycobacterium africanum: Knowns and unknowns

Abstract

Tuberculosis (TB), one of the deadliest threats to human health, is mainly caused by 2 highly related and human-adapted bacteria broadly known as Mycobacterium tuberculosis and Mycobacterium africanum. Whereas M. tuberculosis is widely spread, M. africanum is restricted to West Africa, where it remains a significant cause of tuberculosis. Although several differences have been identified between these 2 pathogens, M. africanum remains a lot less studied than M. tuberculosis. Here, we discuss the genetic, phenotypic, and clinical similarities and differences between strains of M. tuberculosis and M. africanum. We also discuss our current knowledge on the immune response to M. africanum and how it possibly articulates with distinct disease progression and with the geographical restriction attributed to this pathogen. Understanding the functional impact of the diversity existing in TB-causing bacteria, as well as incorporating this diversity in TB research, will contribute to the development of better, more specific approaches to tackle TB.

Fig 1. The phylogenetic structure of the MTBC.

Phylogenetic analysis of 10 MTBC genomes selected to include 1 genome from each of the known MTBC lineages (accession numbers: SRR1162469, ERR2704812, ERR181314, SRR10828835, ERR1193734, SRR8237291, ERR3470572, ERR3470655, ERR756344, and ERR015582). A maximum likelihood tree was created with IQ-TREE v2.1.2 using TVM+F+I (the best-fit model of substitution according to AIC). The tree was coloured using iTOL 6.5.2 with the commonly used colour scheme for the different MTBC lineages: Lineage 1 (L1) in pink; Lineage 2 (L2) in blue; Lineage 3 (L3) in purple; Lineage 4 (L4) in red; Lineage 5 (L5) in brown; Lineage 6 (L6) in green; Lineage 7 (L7) in yellow; Lineage 8 (L8) in light brown; Lineage 9 (L9) in light green; and animal-associated lineages (LA) in black. Strains from L1–L4 and L8 are considered M. tuberculosis sensu stricto and L5, L6, and L9 M. africanum. The scale bar indicates the number of nucleotide substitutions per site. AIC, Akaike information criterion; MTBC, Mycobacterium tuberculosis complex.

Fig 2. Geographic restriction and prevalence of M. africanum.

(A) Geographic distribution of M. africanum lineages 5, 6, and 9 across Africa. Created with https://mapswire.com/africa/political-maps/. (B) Prevalence of lineages 5 and 6, according to the most recent studies conducted in each represented country [–19].

Fig 3. Genetic identity of M. africanum lineages.

Represented are the genetic markers that distinguish M. africanum from M. tuberculosis and lineages 5, 6, and 9 within M. africanum. Of note, since no robust genetic deletions allowing the classification of L9 have been reported, the identification of this lineage is based in specific SNPs. L, lineage; MTBC, Mycobacterium tuberculosis complex; RD, region of difference; SNP, single nucleotide polymorphism.