English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Multidrug-resistant tuberculosis (TB), defined as TB resistant to the two first-line drugs, isoniazid and rifampin, is a serious challenge to global TB eradication efforts. Although mutations in  rpoA  or  rpoC  have been proposed to compensate for this fitness cost due to  rpoB  mutation in rifampicin-resistant  Mycobacterium tuberculosis  mutants, whether the compensatory effect exists and the underlying mechanisms of compensation remain unclear. Here, we used RNA sequencing to investigate the global transcriptional profiles of 6 rifampin-resistant clinical isolates with either single mutation in  rpoB  or dual mutations in  rpoB / rpoC , as well as 3 rifampin-susceptible clinical isolates, trying to prove the potential compensatory effect of  rpoC  by transcriptomic alteration. In rifampin-free conditions,  rpoC  mutation was associated with  M. tuberculosis  upregulation of ribosomal protein-coding genes, dysregulation of growth-related essential genes and balancing the expression of arginine and glutamate synthesis-associated genes. Upon rifampin exposure of  M. tuberculosis  isolates,  rpoC  mutations were associated with the upregulation of the oxidative phosphorylation machinery, which was inhibited in the  rpoB  single mutants, as well as stabilization of the expression of rifampin-regulated essential genes and balancing the expression of genes involved in metabolism of sulfur-containing amino acids. Taken together, our data suggest that  rpoC  mutation may compensate for the fitness defect of rifampicin-resistant  M. tuberculosis  by altering gene expression in response to rifampin exposure.

frontiers in microbiology

Transcriptional Approach for Decoding the Mechanism of rpoC Compensatory Mutations for the Fitness Cost in Rifampicin-Resistant Mycobacterium tuberculosis