Cysteine desulfurase (IscS)-mediated fine-tuning of bioenergetics and SUF expression prevents <i>Mycobacterium tuberculosis</i> hypervirulence.

ABSTRACT: Iron-sulfur (Fe-S) biogenesis requires multiprotein assembly systems, SUF and ISC, in most prokaryotes. M. tuberculosis (Mtb) encodes a complete SUF system, the depletion of which was bactericidal. The ISC operon is truncated to a single gene iscS (cysteine desulfurase), whose function remains uncertain. Here, we show that MtbΔiscS is bioenergetically deficient and hypersensitive to oxidative stress, antibiotics, and hypoxia. MtbΔiscS resisted killing by nitric oxide (NO). RNA sequencing indicates that IscS is important for expressing regulons of DosR and Fe-S-containing transcription factors, WhiB3 and SufR. Unlike wild-type Mtb, MtbΔiscS could not enter a stable persistent state, continued replicating in mice, and show

SUBMITTER: Das M 

PROVIDER: S-EPMC10848736 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature