Profiling of BDQ-induced transcriptome suggests amino acid metabolism and stress responses as alternate mechanisms contributing to BDQ tolerance in Mycobacterium tuberculosis
AKU Student
no
Document Type
Article
Department
Pathology and Laboratory Medicine
Abstract
Under bedaquiline (BDQ) pressure, a temporary persistence period (24-96 h) has been observed, during which H37Rv undergoes metabolic rerouting. However, little is known of transcriptomic changes in BDQ-resistant Mycobacterium tuberculosis (Mtb) isolates during this period. We explored transcriptomic adaptations occurring under inhibitory concentrations of BDQ to delineate pathways supporting drug tolerance and contributing to BDQ resistance. We report overexpression of genes involved in the biosynthesis of L-arginine and L-cysteine in our study isolates. Among stress response genes, genes from the suf operon, involved in Fe-S biogenesis, were upregulated in the study isolates. Differentially expressed amino acid gene clusters likely indicate an under-recognized metabolic pathway contributing to BDQ persistence in the study clinical isolates. Furthermore, Fe-S stress response activated under BDQ pressure may be of particular interest as a mechanism broadly used by Mtb in mitigating different environmental stresses. We propose that these pathways should be explored further as potential drug targets.
Publication (Name of Journal)
Microbiology Spectrum
DOI
10.1128/spectrum.01455-25
Recommended Citation
Saeed, D. K.,
Shakoor, S.,
Ashraf, J.,
Hasan, Z.,
Hasan, R.
(2025). Profiling of BDQ-induced transcriptome suggests amino acid metabolism and stress responses as alternate mechanisms contributing to BDQ tolerance in Mycobacterium tuberculosis. Microbiology Spectrum.
Available at:
https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/1627
Comments
Volume, issue and pagination are not provided by author/publisher.