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Clin Infect Dis DOI:10.1093/cid/cix169

Mycobacterium tuberculosis Whole Genome Sequences From Southern India Suggest Novel Resistance Mechanisms and the Need for Region-Specific Diagnostics.

Publication TypeJournal Article
Year of Publication2017
AuthorsManson, AL, Abeel, T, Galagan, JE, Sundaramurthi, JChandrabos, Salazar, A, Gehrmann, T, Shanmugam, SKumar, Palaniyandi, K, Narayanan, S, Swaminathan, S, Earl, AM
JournalClin Infect Dis
Volume64
Issue11
Pages1494-1501
Date Published2017 Jun 01
ISSN1537-6591
KeywordsAdult, Antitubercular Agents, Base Sequence, Drug Resistance, Multiple, Bacterial, Female, Genetic Variation, Genome, Bacterial, Humans, India, Male, Mutation, Mycobacterium tuberculosis, Phylogeny, Polymerase Chain Reaction, Tuberculosis
Abstract

Background.: India is home to 25% of all tuberculosis cases and the second highest number of multidrug resistant cases worldwide. However, little is known about the genetic diversity and resistance determinants of Indian Mycobacterium tuberculosis, particularly for the primary lineages found in India, lineages 1 and 3.Methods.: We whole genome sequenced 223 randomly selected M. tuberculosis strains from 196 patients within the Tiruvallur and Madurai districts of Tamil Nadu in Southern India. Using comparative genomics, we examined genetic diversity, transmission patterns, and evolution of resistance.Results.: Genomic analyses revealed (11) prevalence of strains from lineages 1 and 3, (11) recent transmission of strains among patients from the same treatment centers, (11) emergence of drug resistance within patients over time, (11) resistance gained in an order typical of strains from different lineages and geographies, (11) underperformance of known resistance-conferring mutations to explain phenotypic resistance in Indian strains relative to studies focused on other geographies, and (11) the possibility that resistance arose through mutations not previously implicated in resistance, or through infections with multiple strains that confound genotype-based prediction of resistance.Conclusions.: In addition to substantially expanding the genomic perspectives of lineages 1 and 3, sequencing and analysis of M. tuberculosis whole genomes from Southern India highlight challenges of infection control and rapid diagnosis of resistant tuberculosis using current technologies. Further studies are needed to fully explore the complement of diversity and resistance determinants within endemic M. tuberculosis populations.

DOI10.1093/cid/cix169
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28498943?dopt=Abstract

Alternate JournalClin. Infect. Dis.
PubMed ID28498943
PubMed Central IDPMC5434337
Grant ListU19 AI110818 / AI / NIAID NIH HHS / United States