Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru
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 Pe...
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Wolters Kluwer Medknow Publications
2020-01-01
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Series: | International Journal of Mycobacteriology |
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doaj-f5c81f79329243759f55356d9d1648eb2020-11-25T03:20:04ZengWolters Kluwer Medknow PublicationsInternational Journal of Mycobacteriology2212-55312212-554X2020-01-019212113710.4103/ijmy.ijmy_27_20Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peruAna Paula VargasAngela A RiosLouis GrandjeanDaniela E KirwanRobert H GilmanPatricia SheenMirko J ZimicBackground: 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.http://www.ijmyco.org/article.asp?issn=2212-5531;year=2020;volume=9;issue=2;spage=121;epage=137;aulast=Vargascompensatory mutationsevolutionrifampicin resistancerpobrpoctuberculosi |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Paula Vargas Angela A Rios Louis Grandjean Daniela E Kirwan Robert H Gilman Patricia Sheen Mirko J Zimic |
spellingShingle |
Ana Paula Vargas Angela A Rios Louis Grandjean Daniela E Kirwan Robert H Gilman Patricia Sheen Mirko J Zimic Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru International Journal of Mycobacteriology compensatory mutations evolution rifampicin resistance rpob rpoc tuberculosi |
author_facet |
Ana Paula Vargas Angela A Rios Louis Grandjean Daniela E Kirwan Robert H Gilman Patricia Sheen Mirko J Zimic |
author_sort |
Ana Paula Vargas |
title |
Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru |
title_short |
Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru |
title_full |
Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru |
title_fullStr |
Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru |
title_full_unstemmed |
Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru |
title_sort |
determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in mycobacterium tuberculosis clinical isolates from peru |
publisher |
Wolters Kluwer Medknow Publications |
series |
International Journal of Mycobacteriology |
issn |
2212-5531 2212-554X |
publishDate |
2020-01-01 |
description |
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. |
topic |
compensatory mutations evolution rifampicin resistance rpob rpoc tuberculosi |
url |
http://www.ijmyco.org/article.asp?issn=2212-5531;year=2020;volume=9;issue=2;spage=121;epage=137;aulast=Vargas |
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