Work

Reactive sulfur species mediated persulfidation cascade regulation mechanism of novel transcription factor SscR Ac in extremophile Acidithiobacillus caldus under extreme copper stress

Year: 2025

Type: article

Abstract: Severe environmental conditions enhance the resilience of biomining microorganisms to elevated metal ion concentrations. The mechanism of how biomining microorganisms resist metal ions is poorly understood. We identified a novel reactive sulfur species (RSS)-sensitive MarR family transcription factor (SscRAc) in Acidithiobacillus caldus by persulfidation proteomics and observed increase in RSS and protein persulfidation levels under 250 mM Cu2+ stress. The deletion of sscRAc gene via CRISPR-Cas9 and conjugative transfer technology enhanced copper sensitivity in A. caldus. ChIP-seq/qRT-PCR revealed that SscRAc regulates copper detoxification by blocking efflux pumps and stimulating RSS metabolism. LC-MS/MS analysis revealed that both Cys74 and Cys78 in SscRAc interact with RSS and undergo persulfidation, resulting in the dissociation of the protein from the promoter-DNA of target genes. Upstream signaling analysis indicated that copper-sensitive repressor CsoRAc, regulated by SscRAc, inversely regulates SscRAc, thereby jointly enabling copper-RSS signal transduction. In conclusion, we identify SscRAc as the first RSS-dependent transcriptional switch directly linking copper toxicity with the persulfidation signaling pathway in extremophiles.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf943