Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru.

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Title: Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru.
Authors: Grandjean, L
Gilman, RH
Iwamoto, T
Köser, CU
Coronel, J
Zimic, M
Török, ME
Ayabina, D
Kendall, M
Fraser, C
Harris, S
Parkhill, J
Peacock, SJ
Moore, DAJ
Colijn, C
Item Type: Journal Article
Abstract: BACKGROUND: Multidrug-resistant tuberculosis poses a major threat to the success of tuberculosis control programs worldwide. Understanding how drug-resistant tuberculosis evolves can inform the development of new therapeutic and preventive strategies. METHODS: Here, we use novel genome-wide analysis techniques to identify polymorphisms that are associated with drug resistance, adaptive evolution and the structure of the phylogenetic tree. A total of 471 samples from different patients collected between 2009 and 2013 in the Lima suburbs of Callao and Lima South were sequenced on the Illumina MiSeq platform with 150bp paired-end reads. After alignment to the reference H37Rv genome, variants were called using standardized methodology. Genome-wide analysis was undertaken using custom written scripts implemented in R software. RESULTS: High quality homoplastic single nucleotide polymorphisms were observed in genes known to confer drug resistance as well as genes in the Mycobacterium tuberculosis ESX secreted protein pathway, pks12, and close to toxin/anti-toxin pairs. Correlation of homoplastic variant sites identified that many were significantly correlated, suggestive of epistasis. Variation in genes coding for ESX secreted proteins also significantly disrupted phylogenetic structure. Mutations in ESX genes in key antigenic epitope positions were also found to disrupt tree topology. CONCLUSION: Variation in these genes have a biologically plausible effect on immunogenicity and virulence. This makes functional characterization warranted to determine the effects of these polymorphisms on bacterial fitness and transmission.
Issue Date: 27-Dec-2017
Date of Acceptance: 1-Dec-2017
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Start Page: e0189838
End Page: e0189838
Journal / Book Title: PLoS ONE
Volume: 12
Issue: 12
Copyright Statement: © 2017 Grandjean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: EP/K026003/1
Keywords: MD Multidisciplinary
General Science & Technology
Publication Status: Published online
Article Number: e0189838
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences

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