title: Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction.
abstract: BACKGROUND
  Mycobacterium africanum, made up of lineages 5 and 6 within the Mycobacterium tuberculosis complex (MTC), causes up to half of all tuberculosis cases in West Africa, but is rarely found outside of this region. The reasons for this geographical restriction remain unknown. Possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of West African ethnicity, and an inability to compete with other lineages outside of West Africa. These latter two hypotheses could be caused by loss of fitness or altered interactions with the host immune system.
  
  
  RESULTS
  We sequenced 92 MTC clinical isolates from Mali, including two lineage 5 and 24 lineage 6 strains. Our genome sequencing assembly, alignment, phylogeny and average nucleotide identity analyses enabled us to identify features that typify lineages 5 and 6 and made clear that these lineages do not constitute a distinct species within the MTC. We found that in Mali, lineage 6 and lineage 4 strains have similar levels of diversity and evolve drug resistance through similar mechanisms. In the process, we identified a putative novel streptomycin resistance mutation. In addition, we found evidence of person-to-person transmission of lineage 6 isolates and showed that lineage 6 is not enriched for mutations in virulence-associated genes.
  
  
  CONCLUSIONS
  This is the largest collection of lineage 5 and 6 whole genome sequences to date, and our assembly and alignment data provide valuable insights into what distinguishes these lineages from other MTC lineages. Lineages 5 and 6 do not appear to be geographically restricted due to an inability to transmit between West African hosts or to an elevated number of mutations in virulence-associated genes. However, lineage-specific mutations, such as mutations in cell wall structure, secretion systems and cofactor biosynthesis, provide alternative mechanisms that may lead to host specificity.
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winglee
authors.affiliation: Genome Sequencing and Analysis Program, The Broad Institute of MIT & Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Abigail
authors.initials: A
authors.lastname: Manson McGuire
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.|Project SEREFO (Centre de Recherche et de Formation sur le VIH/Sida et la Tuberculose)/University of Sciences, Technics and Technologies of Bamako (USTTB), Bamako, Mali.
authors.forename: Mamoudou
authors.initials: M
authors.lastname: Maiga
authors.affiliation: Genome Sequencing and Analysis Program, The Broad Institute of MIT & Harvard, Cambridge, Massachusetts, United States of America.|Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Abeel
authors.affiliation: Genome Sequencing and Analysis Program, The Broad Institute of MIT & Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Terrance
authors.initials: T
authors.lastname: Shea
authors.affiliation: Genome Sequencing and Analysis Program, The Broad Institute of MIT & Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Desjardins
authors.affiliation: Project SEREFO (Centre de Recherche et de Formation sur le VIH/Sida et la Tuberculose)/University of Sciences, Technics and Technologies of Bamako (USTTB), Bamako, Mali.
authors.forename: Bassirou
authors.initials: B
authors.lastname: Diarra
authors.affiliation: Project SEREFO (Centre de Recherche et de Formation sur le VIH/Sida et la Tuberculose)/University of Sciences, Technics and Technologies of Bamako (USTTB), Bamako, Mali.
authors.forename: Bocar
authors.initials: B
authors.lastname: Baya
authors.affiliation: Project SEREFO (Centre de Recherche et de Formation sur le VIH/Sida et la Tuberculose)/University of Sciences, Technics and Technologies of Bamako (USTTB), Bamako, Mali.
authors.forename: Moumine
authors.initials: M
authors.lastname: Sanogo
authors.affiliation: Project SEREFO (Centre de Recherche et de Formation sur le VIH/Sida et la Tuberculose)/University of Sciences, Technics and Technologies of Bamako (USTTB), Bamako, Mali.
authors.forename: Souleymane
authors.initials: S
authors.lastname: Diallo
authors.affiliation: Genome Sequencing and Analysis Program, The Broad Institute of MIT & Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Ashlee M
authors.initials: AM
authors.lastname: Earl
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
mesh_terms: D016680:Genome, Bacterial; D006801:Humans; D008302:Mali / Q000453:epidemiology; D009161:Mycobacterium / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D009164:Mycobacterium Infections / Q000453:epidemiology* / Q000382:microbiology*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011544:Pseudogenes; D013045:Species Specificity; D014774:Virulence