Whole-genome sequencing illuminates the evolution and spread of multidrug-resistant tuberculosis in Southwest Nigeria

Madikay Senghore, Jacob Otu, Adam Witney, Florian Gehre, Emma L. Doughty, Gemma L. Kaye, Phillip Butcher, Kayode Salako, Aderemi Kehinde, Nneka Onyejepu, Emmanuel Idigbe, Tumani Corrah, Bouke de Jong, Mark J. Pollee, Martin Antonio

Research output: Contribution to journalA1: Web of Science-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 multidrug resistance in this region.

Original languageEnglish
Article number0184510
JournalPLoS ONE
Volume12
Issue number9
Number of pages12
ISSN1932-6203
DOIs
Publication statusPublished - 2017

Keywords

  • MYCOBACTERIUM-TUBERCULOSIS
  • MOLECULAR EPIDEMIOLOGY
  • TRANSMISSION
  • DIVERSITY
  • CAMEROON
  • COMPLEX
  • WORLD
  • TOOL

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