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

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dc.contributor.author Grandjean, Louis
dc.contributor.author Gilman, Robert H.
dc.contributor.author Iwamoto, Tomatada
dc.contributor.author Köser, Claudio U.
dc.contributor.author Coronel, Jorge
dc.contributor.author Zimic, Mirko
dc.contributor.author Török, M. Estee
dc.contributor.author Ayabina, Diepreye
dc.contributor.author Kendall, Michelle
dc.contributor.author Fraser, Christophe
dc.contributor.author Harris, Simon
dc.contributor.author Parkhill, Julian
dc.contributor.author Peacock, Sharon J.
dc.contributor.author Moore, David A. J.
dc.contributor.author Colijn, Caroline
dc.date.accessioned 2019-01-25T15:02:21Z
dc.date.available 2019-01-25T15:02:21Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4625
dc.description.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. en_US
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartof urn:issn:1932-6203
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Polymorphism, Single Nucleotide en_US
dc.subject Adult en_US
dc.subject Drug Resistance, Multiple, Bacterial/genetics en_US
dc.subject Female en_US
dc.subject Genes, Bacterial en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Mutation en_US
dc.subject Mycobacterium tuberculosis/drug effects/genetics en_US
dc.subject Peru en_US
dc.subject Phylogeny en_US
dc.subject Tuberculosis, Multidrug-Resistant/microbiology en_US
dc.subject Young Adult en_US
dc.title Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1371/journal.pone.0189838
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE

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