Rifampicin and rifabutin resistance in 1003 Mycobacterium tuberculosis clinical isolates.

The Journal of Antimicrobial Chemotherapy
Maha R FarhatMegan Murray

Abstract

Drug-resistant TB remains a public health challenge. Rifamycins are among the most potent anti-TB drugs. They are known to target the RpoB subunit of RNA polymerase; however, our understanding of how rifamycin resistance is genetically encoded remains incomplete. Here we investigated rpoB genetic diversity and cross-resistance between the two rifamycin drugs rifampicin and rifabutin. We performed WGS of 1003 Mycobacterium tuberculosis clinical isolates and determined MICs of both rifamycin agents on 7H10 agar using the indirect proportion method. We generated rpoB mutants in a laboratory strain and measured their antibiotic susceptibility using the alamarBlue reduction assay. Of the 1003 isolates, 766 were rifampicin resistant and 210 (27%) of these were rifabutin susceptible; 102/210 isolates had the rpoB mutation D435V (Escherichia coli D516V). Isolates with discordant resistance were 17.2 times more likely to harbour a D435V mutation than those resistant to both agents (OR 17.2, 95% CI 10.5-27.9, P value <10-40). Compared with WT, the D435V in vitro mutant had an increased IC50 of both rifamycins; however, in both cases to a lesser degree than the S450L (E. coli S531L) mutation. The observation that the rpoB D435V mutation p...Continue Reading

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Citations

Jan 30, 2020·Proceedings of the National Academy of Sciences of the United States of America·Douglas L HusebyDiarmaid Hughes
Mar 4, 2021·MBio·J A JuddK M Derbyshire
May 6, 2021·Scientific Reports·David Santos-LazaroZully M Puyen
Jul 11, 2021·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Mehmood QadirRani Faryal
Oct 28, 2021·American Journal of Respiratory and Critical Care Medicine·Sachin R AtreMaha R Farhat

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