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. 2017 Sep 19;12(9):e0184510.
doi: 10.1371/journal.pone.0184510. eCollection 2017.

Whole-genome Sequencing Illuminates the Evolution and Spread of Multidrug-Resistant Tuberculosis in Southwest Nigeria

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Free PMC article

Whole-genome Sequencing Illuminates the Evolution and Spread of Multidrug-Resistant Tuberculosis in Southwest Nigeria

Madikay Senghore et al. PLoS One. .
Free PMC article

Abstract

Nigeria has an emerging problem with multidrug-resistant tuberculosis (MDR-TB). Whole-genome sequencing was used to understand the epidemiology of tuberculosis and genetics of multi-drug resistance among patients from two tertiary referral centers in Southwest Nigeria. In line with previous molecular epidemiology studies, most isolates of Mycobacterium tuberculosis from this dataset belonged to the Cameroon clade within the Euro-American lineage. Phylogenetic analysis showed this clade was undergoing clonal expansion in this region, and suggests that it was involved in community transmission of sensitive and multidrug-resistant tuberculosis. Five patients enrolled for retreatment were infected with pre-extensively drug resistant (pre-XDR) due to fluoroquinolone resistance in isolates from the Cameroon clade. In all five cases resistance was conferred through a mutation in the gyrA gene. In some patients, genomic changes occurred in bacterial isolates during the course of treatment that potentially led to decreased drug susceptibility. We conclude that inter-patient transmission of resistant isolates, principally from the Cameroon clade, contributes to the spread of MDR-TB in this setting, underscoring the urgent need to curb the spread of multi-drug resistance in this region.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Maximum likelihood phylogeny of Mtb isolated from patients with active pulmonary TB.
Branches are coloured by lineage and tips are coloured by the sub-clades within the lineages. A star marks almost identical genomes (<3 SNVs difference) isolated from different patients. Adjacent data links strains to patient metadata: MDR and pre-XDR status, treatment status, HIV status, sex and recruitment site and date of sample reception.
Fig 2
Fig 2. Microevolution of Mtb within patients during the course of treatment.
Phylogenetic tree is linked to resistance profile of isolates that were paired with at least one near-identical genome (<3 SNVs difference). These genomes represent isolates from patients that were samples at least twice during the course of treatment as well as almost identical genomes from different patients. The resistance profiles for Streptomycin (Str), Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB), Flouroquinolones (FQ), Capreomycin (CAP), KANAMYCIN (KAN) and Ethionamide (ETH) are shown. The presence of resistance mutations to each drug are listed next to a bar indicating phenotypic susceptibility.
Fig 3
Fig 3. Molecular mechanisms of resistance to first- and second-line anti-TB drugs.
A heatmap showing the phenotypic susceptibility profiles to first- and second-line anti-TB drugs and the presence of known resistance mutations. Blue = phenotypically susceptible, Red = phenotypically resistant, Black = presence of resistance mutation, white = absence of resistance mutation and grey = no phenotypic testing.

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