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Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru.

Vargas, AP; Rios, AA; Grandjean, L; Kirwan, DE; Gilman, RH; Sheen, P; Zimic, MJ (2020) Determination of potentially novel compensatory mutations in rpoc associated with rifampin resistance and rpob mutations in Mycobacterium tuberculosis Clinical isolates from peru. Int J Mycobacteriol, 9 (2). pp. 121-137. ISSN 2212-554X https://doi.org/10.4103/ijmy.ijmy_27_20
SGUL Authors: Kirwan, Daniela Elisa

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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.

Item Type: Article
Additional Information: This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. © 2020 International Journal of Mycobacteriology
Keywords: Compensatory mutations, evolution, rifampicin resistance, rpoB, rpoC, tuberculosi, Compensatory mutations, evolution, rifampicin resistance, rpoB, rpoC, tuberculosi
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Int J Mycobacteriol
ISSN: 2212-554X
Language: eng
Dates:
DateEvent
29 May 2020Published Online
4 April 2020Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-Share Alike 4.0
Projects:
Project IDFunderFunder ID
099805/Z/12/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
0687‑01‑10Grand Challenge CanadaUNSPECIFIED
PubMed ID: 32474533
Web of Science ID: WOS:000542146200003
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112305
Publisher's version: https://doi.org/10.4103/ijmy.ijmy_27_20

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