A small RNA promotes siderophore production through transcriptional and metabolic remodeling

Abstract

Siderophores are essential factors for iron (Fe) acquisition in bacteria during colonization and infection of eukaryotic hosts, which restrain iron access through iron-binding protein, such as lactoferrin and transferrin. The synthesis of siderophores by Escherichia coli is considered to be fully regulated at the transcriptional level by the Fe-responsive transcriptional repressor Fur. Here we characterized two different pathways that promote the production of the siderophore enterobactin via the action of the small RNA RyhB. First, RyhB is required for normal expression of an important enterobactin biosynthesis polycistron, entCEBAH. Second, RyhB directly represses the translation of cysE, which encodes a serine acetyltransferase that uses serine as a substrate for cysteine biosynthesis. Reduction of CysE activity by RyhB allows serine to be used as building blocks for enterobactin synthesis through the nonribosomal peptide synthesis pathway. Thus, RyhB plays an essential role in siderophore production and may modulate bacterial virulence through optimization of siderophore production.

Role of the Salmonella enterica serovar Typhi Fur regulator and small RNAs RfrA and RfrB in iron homeostasis and interaction with host cells

“…This could be explained by the iron content of the CAS agar plates (10 mM), which was high enough to activate Fur and to trigger Fur-mediated repression of the sRNAs. The highest production of siderophore observed in the triple mutant is consistent with results in E. coli, where in minimal medium containing 1 mM or more of iron, production of siderophore is higher in the double fur/ryhB mutant than in the wild-type and the fur mutant strains (Salvail et al, 2010).…”

“…By inhibiting the synthesis of these proteins, RyhB promotes availability of iron for essential iron-using proteins required for biological processes including respiration, the tricarboxylic acid cycle, oxygen transport and DNA biosynthesis. Recently, it was shown that RyhB promotes synthesis of the siderophore enterobactin in E. coli K-12 (Salvail et al, 2010).…”

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

“…By inhibiting the synthesis of these proteins under iron-limited conditions, RyhB promotes availability of iron for essential iron-using proteins required for many biological processes (respiration, oxygen transport, and DNA biosynthesis) (17). RyhB has also been shown to promote synthesis of the siderophore enterobactin in nonpathogenic E. coli K-12 (18,19). Siderophores are high-affinity iron-chelating molecules that contribute to bacterial survival by sequestering iron from the host.…”

“…Siderophores are high-affinity iron-chelating molecules that contribute to bacterial survival by sequestering iron from the host. RyhB-dependent regulation of enterobactin siderophore production is mediated by (i) repressing the translation of cysE mRNA, which allows more serine to be used for enterobactin production (19); and (ii) activating shiA mRNA translation to increase shikimate (a metabolic precursor of enterobactin biosynthesis) acquisition from the environment (18). RyhB is also required for normal expression of the enterobactin biosynthesis polycistron, entCEBAH (19).…”

Noncanonical repression of translation initiation through small RNA recruitment of the RNA chaperone Hfq

“…This post-transcriptional regulation allows the cell to preserve sufficient intracellular Fe for essential cellular functions (Massé et al 2005;Jacques et al 2006;Salvail et al 2010). One of the first described targets of RyhB was the polycistronic mRNA sdhCDAB (Massé and Gottesman 2002), which encodes the four subunits of Fe-dependent succinate dehydrogenase of the tricarboxylic acid (TCA) cycle.…”