Activation of the Spx redox sensor counters cysteine-driven Fe(II) depletion under disulfide stress
All cells have a pool of low molecular weight thiols, such as cysteine, glutathione, bacillithiol, and coenzyme A, to maintain redox balance under oxidative and disulfide stress. Among these, cysteine is a very effective thiol but is highly reactive, and its intracellular concentration must be tightly regulated. In <i>S. aureus</i> , we found that cysteine accumulates intracellularly during disulfide stress and if left unchecked, can inadvertently deplete cytosolic Fe(II), leading to growth inhibition. To prevent cysteine toxicity, <i>S. aureus</i> activates the global regulator Spx, which rapidly induces genes that restore thiol homeostasis and limits cysteine accumulation.
Authors
- Svetlana Romanova (ORCID: https://orcid.org/0000-0001-7506-4699)
- Andrew J. Monteith (ORCID: https://orcid.org/0000-0002-7259-6574)
- Sujata S. Chaudhari (ORCID: https://orcid.org/0000-0002-9609-152X)
- Vinai C. Thomas (ORCID: https://orcid.org/0000-0002-7886-0727)
- Abdulelah A. Alqarzaee (ORCID: https://orcid.org/0000-0003-0000-9040)
- Dorte Frees (ORCID: https://orcid.org/0000-0003-4946-2890)
- Asha Hall (ORCID: https://orcid.org/0000-0002-2121-2999)
- Amanda Collins (ORCID: https://orcid.org/0000-0002-4653-7095)
- Sasmita Panda
Institutions
- University of Copenhagen (DK)
- Nebraska Medical Center (US)
- University of Nebraska Medical Center (US)
- University of Tennessee at Knoxville (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2025-12-03
- DOI
- https://doi.org/10.64898/2025.12.03.692063
- Primary Topic
- Sulfur Compounds in Biology
- Type
- article
- Field-Weighted Citation Impact
- 0.00