TitleCysteine desulfurase (IscS)-mediated fine-tuning of bioenergetics and SUF expression prevents hypervirulence.
Publication TypeJournal Article
Year of Publication2023
AuthorsDas M, Sreedharan S, Shee S, Malhotra N, Nandy M, Banerjee U, Kohli S, Rajmani RS, Chandra N, Seshasayee ASai Narain, Laxman S, Singh A
JournalSci Adv
Date Published2023 Dec 15
KeywordsAnimals, Energy Metabolism, Escherichia coli, Iron-Sulfur Proteins, Mice, Mycobacterium tuberculosis

Iron-sulfur (Fe-S) biogenesis requires multiprotein assembly systems, SUF and ISC, in most prokaryotes. () encodes a complete SUF system, the depletion of which was bactericidal. The ISC operon is truncated to a single gene (cysteine desulfurase), whose function remains uncertain. Here, we show that Δ is bioenergetically deficient and hypersensitive to oxidative stress, antibiotics, and hypoxia. Δ 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 , Δ could not enter a stable persistent state, continued replicating in mice, and showed hypervirulence. The operon was overexpressed in Δ during infection in a NO-dependent manner. Suppressing expression in Δ either by CRISPR interference or upon infection in inducible NO-deficient mice arrests hypervirulence. Together, redesigned the ISC system to "fine-tune" the expression of SUF machinery for establishing persistence without causing detrimental disease in the host.

Alternate JournalSci Adv
PubMed ID38091389