Pleomorphic effects of three small-molecule inhibitors on transcription elongation by <i>Mycobacterium tuberculosis</i> RNA polymerase.

ABSTRACT: The Mycobacterium tuberculosis RNA polymerase (MtbRNAP) is the target of the first-line anti-tuberculosis inhibitor rifampin; however, the emergence of rifampin resistance necessitates the development of new antibiotics. Here, we communicate the first single-molecule characterization of MtbRNAP elongation and its inhibition by three diverse small-molecule inhibitors: N(α)-aroyl-N-aryl-phenylalaninamide (D-IX216), streptolydigin (Stl), and pseudouridimycin (PUM) using high-resolution optical tweezers. Compared to Escherichia coli RNA polymerase (EcoRNAP), MtbRNAP transcribes more slowly, has similar mechanical robustness, and only weakly recognizes E. coli pause sequences. The three small-molecule inhibitors of MtbRNAP exhibit strikingly different effects on transcripti

SUBMITTER: Herrera-Asmat O 

PROVIDER: S-EPMC12558654 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature