Universidad Peruana Cayetano Heredia

Determination of potentially novel compensatory mutations in rpoC associated with rifampin resistance and rpoB mutations in Mycobacterium tuberculosis Clinical isolates from Peru

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dc.contributor.author Vargas Ruiz, Ana Paula
dc.contributor.author Rios, A.
dc.contributor.author Grandjean, Louis
dc.contributor.author Kirwan, D.
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.date.accessioned 2020-12-14T16:11:07Z
dc.date.available 2020-12-14T16:11:07Z
dc.date.issued 2020
dc.identifier.uri https://hdl.handle.net/20.500.12866/8844
dc.description.abstract Background: Rifampicin (RIF) resistance in Mycobacterium tuberculosis is frequently caused by mutations in the rpoB gene. These mutations are associated with a fitness cost, which can be overcome by compensatory mutations in other genes, among which rpoC may be the most important. We analyzed 469 Peruvian M. tuberculosis clinical isolates to identify compensatory mutations in rpoC/rpoA associated with RIF resistance. Methods: The M. tuberculosis isolates were collected and tested for RIF susceptibility and spoligotyping. Samples were sequenced and aligned to the reference genome to identify mutations. By analyzing the sequences and the metadata, we identified a list of rpoC mutations exclusively associated with RIF resistance and mutations in rpoB. We then evaluated the distribution of these mutations along the protein sequence and tridimensional structure. Results: One hundred and twenty-five strains were RIF susceptible and 346 were resistant. We identified 35 potential new compensatory mutations, some of which were distributed on the interface surface between rpoB and rpoC, arising in clusters and suggesting the presence of hotspots for compensatory mutations. Conclusion: This study identifies 35 putative novel compensatory mutations in the β' subunit of M. tuberculosis RNApol. Six of these (S428T, L507V, A734V, I997V, and V1252LM) are considered most likely to have a compensatory role, as they fall in the interaction zone of the two subunits and the mutation did not lead to any change in the protein's physical-chemical properties. © 2020 International Journal of Mycobacteriology | Published by Wolters Kluwer - Medknow. en_US
dc.language.iso eng
dc.publisher Medknow Publications
dc.relation.ispartofseries International Journal of Mycobacteriology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Compensatory mutations en_US
dc.subject evolution en_US
dc.subject rifampicin resistance en_US
dc.subject rpoB en_US
dc.subject rpoC en_US
dc.subject tuberculosi en_US
dc.title Determination of potentially novel compensatory mutations in rpoC associated with rifampin resistance and rpoB mutations in Mycobacterium tuberculosis Clinical isolates from Peru en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.4103/ijmy.ijmy_27_20
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.relation.issn 2212-554X


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