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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the β′ subunit of RNA polymerase
Molecular Microbiology, Volume 91, No. 6, Year 2014
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Description
Rifampicin resistance, a defining attribute of multidrug-resistant tuberculosis, is conferred by mutations in the β subunit of RNA polymerase. Sequencing of rifampicin-resistant (RIF-R) clinical isolates of Mycobacterium tuberculosis revealed, in addition to RIF-R mutations, enrichment of potential compensatory mutations around the double-psi β-barrel domain of the β′ subunit comprising the catalytic site and the exit tunnel for newly synthesized RNA. Sequential introduction of the resistance allele followed by the compensatory allele in isogenic Mycobacterium smegmatis showed that these mutations respectively caused and compensated a starvation enhanced growth defect by altering RNA polymerase activity. While specific combinations of resistance and compensatory alleles converged in divergent lineages, other combinations recurred among related isolates suggesting transmission of compensated RIF-R strains. These findings suggest nutrient poor growth conditions impose larger selective pressure on RIF-R organisms that results in the selection of compensatory mutations in a domain involved in catalysis and starvation control of RNA polymerase transcription. © 2014 John Wiley & Sons Ltd.
Authors & Co-Authors
Song, Taeksun
South Korea, Changwon
International Tuberculosis Research Center
Park, Yumi
South Korea, Changwon
International Tuberculosis Research Center
Shamputa, Isdore Chola
United States, Bethesda
National Institutes of Health Nih
Jeon, Han-seung
South Korea, Changwon
International Tuberculosis Research Center
Choi, Hongjo
South Korea, Changwon
International Tuberculosis Research Center
Lee, Myungsun
South Korea, Changwon
International Tuberculosis Research Center
Batalov, Serge
United States, San Diego
The Genomics Institute of the Novartis Research Foundation
Yusim, Karina
United States, Los Alamos
Los Alamos National Laboratory
Via, L. E.
United States, Bethesda
National Institutes of Health Nih
Boshoff, Helena Ingrid M.
United States, Bethesda
National Institutes of Health Nih
Korber, Bette T.
United States, Los Alamos
Los Alamos National Laboratory
Barry, Clifton Earl
South Korea, Changwon
International Tuberculosis Research Center
United States, Bethesda
National Institutes of Health Nih
Cho, Sangnae Ray
South Korea, Changwon
International Tuberculosis Research Center
South Korea, Seoul
Yonsei University College of Medicine
Statistics
Citations: 69
Authors: 13
Affiliations: 6
Identifiers
Doi:
10.1111/mmi.12520
ISSN:
13652958
Research Areas
Cancer
Genetics And Genomics