Evolutionary history and spread of the Mycobacterium tuberculosis Latin American and Mediterranean (L4.3/LAM) sublineage, Tunisia

BACKGROUND: To infer the origin and spread of the Mycobacterium tuberculosis Latin American and Mediterranean (L4.3/LAM) sublineage in a Mediterranean country, Tunisia, where it predominates. METHODS: We combined Bayesian (STRUCTURE) and maximum likelihood (MIGRAINE) estimation approaches based on a global 24-loci mycobacterial interspersed repetitive units-variable numbers of tandem repeats (MIRU-VNTR24) genotyping dataset consisting of 1573 L4.3/LAM clinical strains from four continents, including 252 isolates originating from Tunisia. RESULTS: Phylogenetic analyses coupled with Bayesian estimations suggested that the most predominant L4.3/LAM subpopulation in Tunisia (65.07%), which is dominated by a single clonal complex, TUN4.3_CC1 (94.51%), has evolved from an ancestral pool that is restricted to Europe and Africa, contrasting with the remaining L4.3/LAM subpopulations whose ancestry was traced all over the word. Maximum likelihood analysis revealed that TUN4.3_CC1 has been undergoing a demographic expansion since 131 years ago (CI95%: 90.7-205), thus explaining its preponderance relative to the second most predominant CC, TUN4.3_CC2, whose population was found under contraction. CONCLUSIONS: The preponderance of L4.3/LAM in Tunisia stems from a 130-year expansion process of a locally evolved clone.