title: Latin-American-Mediterranean lineage of Mycobacterium tuberculosis: Human traces across pathogen's phylogeography.
abstract: Currently, Mycobacterium tuberculosis isolates of Latin-American Mediterranean (LAM) family may be detected far beyond the geographic areas that coined its name 15years ago. Here, we established the framework phylogeny of this geographically intriguing and pathobiologically important mycobacterial lineage and hypothesized how human demographics and migration influenced its phylogeography. Phylogenetic analysis of LAM isolates from all continents based on 24 variable number of tandem repeats (VNTR) loci and other markers identified three global sublineages with certain geographic affinities and defined by large deletions RD115, RD174, and by spoligotype SIT33. One minor sublineage (spoligotype SIT388) appears endemic in Japan. One-locus VNTR signatures were established for sublineages and served for their search in published literature and geographic mapping. We suggest that the LAM family originated in the Western Mediterranean region. The most widespread RD115 sublineage seems the most ancient and encompasses genetically and geographically distant branches, including extremely drug resistant KZN in South Africa and LAM-RUS recently widespread across Northern Eurasia. The RD174 sublineage likely started its active spread in Brazil; its earlier branch is relatively dominated by isolates from South America and the derived one is dominated by Portuguese and South/Southeastern African isolates. The relatively most recent SIT33-sublineage is marked with enigmatic gaps and peaks across the Americas and includes South African clade F11/RD761, which likely emerged within the SIT33 subpopulation after its arrival to Africa. In addition to SIT388-sublineage, other deeply rooted, endemic LAM sublineages may exist that remain to be discovered. As a general conclusion, human mass migration appears to be the major factor that shaped the M. tuberculosis phylogeography over large time-spans.
authors.affiliation: St. Petersburg Pasteur Institute, 14 Mira Street, St. Petersburg 197101, Russia. Electronic address: imokrousov@mail.ru.
authors.forename: Igor
authors.initials: I
authors.lastname: Mokrousov
authors.affiliation: St. Petersburg Pasteur Institute, 14 Mira Street, St. Petersburg 197101, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Vyazovaya
authors.affiliation: Kobe Institute of Health, 4-6 Minatojima-nakamachi, Chuo-ku, Kobe 650-0046, Japan.
authors.forename: Tomotada
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Aitkhozhin Institute of Molecular Biology and Biochemistry, 86, Dosmuhamedov str., Almaty 050012, Kazakhstan.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Skiba
authors.affiliation: Latvian Biomedical Research and Study Centre, Ratsupites Street 1, Riga LV-1067, Latvia; Center of Tuberculosis and Lung Diseases, Riga East University Hospital, Stopinu p., Riga LV-2118, Latvia.
authors.forename: Ilva
authors.initials: I
authors.lastname: Pole
authors.affiliation: Scientific Center of Family Health and Reproductive Problems, Irkutsk 664003, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Zhdanova
authors.affiliation: Kobe Institute of Health, 4-6 Minatojima-nakamachi, Chuo-ku, Kobe 650-0046, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Arikawa
authors.affiliation: Scientific Center of Family Health and Reproductive Problems, Irkutsk 664003, Russia.
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Sinkov
authors.affiliation: Ural Research Institute of Phthisiopulmonology, 50 22go Partsiezda str., Ekaterinburg 620039, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Umpeleva
authors.affiliation: The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G Bonchev str., Sofia 1113, Bulgaria.
authors.forename: Violeta
authors.initials: V
authors.lastname: Valcheva
authors.affiliation: Central Research Institute for Epidemiology, 3A Novogireevskaya str., Moscow 111123, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarez Figueroa
authors.affiliation: Latvian Biomedical Research and Study Centre, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Renate
authors.initials: R
authors.lastname: Ranka
authors.affiliation: Latvian Biomedical Research and Study Centre, Ratsupites Street 1, Riga LV-1067, Latvia.
authors.forename: Inta
authors.initials: I
authors.lastname: Jansone
authors.affiliation: Scientific Center of Family Health and Reproductive Problems, Irkutsk 664003, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Ogarkov
authors.affiliation: Research Institute of Phthisiopulmonology, 2-4 Ligovsky prospect, St. Petersburg 191036, Russia.
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Zhuravlev
authors.affiliation: St. Petersburg Pasteur Institute, 14 Mira Street, St. Petersburg 197101, Russia; Research Institute of Phthisiopulmonology, 2-4 Ligovsky prospect, St. Petersburg 191036, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Narvskaya
mesh_terms: D024881:Drug Resistance, Bacterial; D008040:Genetic Linkage; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D019083:Mediterranean Region; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity; D010802:Phylogeny; D058974:Phylogeography; D013020:South America
keywords: Latin-American-Mediterranean lineage; Mycobacterium tuberculosis; Phylogeny; Phylogeography