The structure of salmochelins: C-glucosylated enterobactins of Salmonella enterica^§

Abstract

Salmochelins represent novel carbohydrate containing catecholate siderophores, which are excreted by Salmonella enterica and uropathogenic Escherichia coli strains under low-iron stress. While previous analytical data showed salmochelins to contain 2,3-dihydroxybenzoyl-L-serine and glucose, the molecular structure remained elusive. Structure elucidation with electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), GC-MS and 2D-NMR now revealed that salmochelins are enterobactin-related compounds, which are beta-C-glucosylated at the 5-position of a 2,3-dihydroxybenzoyl residue. The key compound salmochelin S4 is a twofold beta-C-glucosylated enterobactin analogue. Comparison of partial structures of salmochelin with a C-glycosylated compound previously characterized by another group strongly suggest that salmochelins represent the long sought compounds termed Salmonella resistance factors (SRF) or pacifarins. Transformation of iro-genes into enterobactin-producing E. coli K12 confers the ability to produce salmochelins. A detailed analysis proved iroB to be the sole gene with glycosyltransferase activity necessary for salmochelin production. Salmochelins compared to enterobactin are the better siderophores in the presence of serum albumin. This may indicate for salmochelins a considerably more important role for pathogenic processes in certain Escherichia coli and Salmonella infections than formerly assigned to enterobactin. This conclusion is supported by the location of the iro genes on pathogenicity islands of uropathogenic E. coli strains.

The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2

“…Rather than Ent, iroAharboring bacteria secrete a mixture of salmochelins S4 and S2 ( Fig. 1 A), which are macrocyclic and linearized versions of diglucosylated Ent, respectively (16,17). We have shown that glucosylation and linearization of Ent decrease its propensity to partition into lipid bilayers, which might be advantageous for iron scavenging in a membrane-rich microenvironment (18).…”

Iron metabolism at the host pathogen interface: Lipocalin 2 and the pathogen-associated iroA gene cluster

“…Molecular characterization demonstrated that salmochelins are glucosylated versions of enterobactin (Bister et al, 2004). There are several potential advantages of enterobactin glucosylation.…”

Accessorizing natural products: Adding to nature's toolbox

“…This ability is necessary for their survival and proliferation in the iron-poor environment of tissues and cells, and, as a result, siderophores are often considered potential virulence factors. Salmochelins in particular seem to be superior siderophores, compared with enterobactin, in the presence of serum albumin; therefore, it has been suggested that salmochelins may play a significant role in some infections (10).…”