YeiE regulates YeiH to implement sulfite stress resistance in Salmonella enterica serotype Typhimurium

Abstract

Sulfites are toxic reactive sulfur species that are ubiquitous in nature. Bacteria are exposed to sulfites during the metabolism of sulfur-containing amino acids, during respiration using sulfur-containing electron acceptors, in host environments, and as food preservatives. Despite their broad distribution, the mechanisms bacteria use to resist the toxic effects of sulfites are poorly understood. Recent work showed that the LysR-type transcriptional regulator YeiE binds to sulfite to activate sulfite reduction gene expression. Using the model enteric pathogen, Salmonella enterica serotype Typhimurium, we show that YeiE is an autoregulator whose expression is enhanced by sulfite. We demonstrate here that the mechanism of sulfite stress resistance is distinct from pathways of sulfur assimilation for cysteine biogenesis. YeiE is necessary for survival in sulfite stress due to its regulation of the poorly characterized adjacent gene, yeiH. A yeiH deletion mutant is more sensitive to the growth-inhibiting effects of sulfite than a yeiE deletion mutant, demonstrating YeiH is the primary driver of sulfite stress resistance in vitro. This work provides a fundamental advance in understanding the sulfite stress response in bacteria with broad implications for food safety and host-pathogen interactions.