Salmonella has evolved complicated regulatory systems to regulate the expression of virulence determinants that are acquired by horizontal gene transfer in response to various environmental niches. Among these, small RNA (sRNA)-mediated regulation exhibits unique features, distinct from those of protein factor-mediated regulation, which may provide benefits for a pathogen coping with the complex stress conditions encountered during host infection. Specifically, iron acquisition by this pathogenic bacterium is important for cellular processes such as energy metabolism and DNA replication. Many studies on the role of RyhB sRNA have begun to unveil the essential nature of iron acquisition in allowing the organism to persist and develop pathogenicity. The Salmonella genome encodes two RyhB paralogs, RyhB-1 and RyhB-2, which are known to act singularly or together on target expression. Based on the mechanism of Escherichia coli RyhB function, this review proposes a possible model to show how two Salmonella RyhB paralogs regulate the level of target mRNAs by sensing environmental inputs or conditions. This review also describes the involvement of Salmonella RyhBs in diverse functions including nitrate homeostasis, adaptive system to oxidative stress, and intracellular survival. Thus, the two Salmonella RyhBs play a critical role in the regulation of gene expression that appears to be essential for persistence and pathogenesis of Salmonella spp.
