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PLoS Negl Trop Dis DOI:10.1371/journal.pntd.0004332

Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction.

Publication TypeJournal Article
Year of Publication2016
AuthorsWinglee, K, McGuire, AManson, Maiga, M, Abeel, T, Shea, T, Desjardins, CA, Diarra, B, Baya, B, Sanogo, M, Diallo, S, Earl, AM, Bishai, WR
JournalPLoS Negl Trop Dis
Date Published2016 Jan
KeywordsGenome, Bacterial, Humans, Mali, Mycobacterium, Mycobacterium Infections, Phylogeny, Polymorphism, Single Nucleotide, Pseudogenes, Species Specificity, Virulence

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.

METHODOLOGY/PRINCIPAL FINDINGS: 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.


Alternate JournalPLoS Negl Trop Dis
PubMed ID26751217
PubMed Central IDPMC4713829
Grant ListAI097138 / AI / NIAID NIH HHS / United States
R01 AI110386 / AI / NIAID NIH HHS / United States
AI036973 / AI / NIAID NIH HHS / United States
HHSN272200900018C / / PHS HHS / United States
/ / Howard Hughes Medical Institute / United States
U19AI110818 / AI / NIAID NIH HHS / United States
AI037856 / AI / NIAID NIH HHS / United States
T32 GM008752 / GM / NIGMS NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States