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PLoS Negl Trop Dis. 2016 Jan 11;10(1):e0004332. doi: 10.1371/journal.pntd.0004332. eCollection 2016 Jan.

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

Author information

1
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
2
Genome Sequencing and Analysis Program, The Broad Institute of MIT & Harvard, Cambridge, Massachusetts, United States of America.
3
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.
4
Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.

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.

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.

PMID:
26751217
PMCID:
PMC4713829
DOI:
10.1371/journal.pntd.0004332
[Indexed for MEDLINE]
Free PMC Article

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