DsbL and DsbI contribute to periplasmic disulfide bond formation in Salmonella enterica serovar Typhimurium

Abstract

Disulfide bond formation in periplasmic proteins is catalysed by the DsbA/DsbB system in most Gram-negative bacteria. Salmonella enterica serovar Typhimurium also encodes a paralogous pair of proteins to DsbA and DsbB, DsbL and DsbI, respectively, downstream of a periplasmic arylsulfate sulfotransferase (ASST). We show that DsbL and DsbI function as a redox pair contributing to periplasmic disulfide bond formation and, as such, affect transcription of the Salmonella pathogenicity island 1 (SPI1) type three secretion system genes and activation of the RcsCDB system, as well as ASST activity. In contrast to DsbA/DsbB, however, the DsbL/DsbI system cannot catalyse the disulfide bond formation required for flagellar assembly. Phylogenic analysis suggests that the assT dsbL dsbI genes are ancestral in the Enterobacteriaceae, but have been lost in many lineages. Deletion of assT confers no virulence defect during acute Salmonella infection of mice.

Transcriptional Regulation of the assT - dsbL - dsbI Gene Cluster in Salmonella enterica Serovar Typhi IMSS-1 Depends on LeuO, H-NS, and Specific Growth Conditions

“…Moreover, in S. Typhimurium assT and dsbL have been reported as virulence factors in Nramp1-resistant mice, and a mutation in assT results in attenuated virulence in Edwardsiella tarda in a fish model (38,45). However, assT mutants in S. Typhimurium did not affect the pathogenesis in BALB/c mice or assT or dsbL-dsbI gene deletions during UPEC colonization in the mouse urinary tract infection model (40,62).…”

“…However, in S. Typhimurium, dsbL expression can occur independently from assT (40). We show that in S. Typhi IMSS-1, the transcriptional regulation of the assT-dsbL-dsbI cluster depends on global regulatory proteins and specific growth conditions.…”

“…These sulfotransferases use 3=-phosphoadenosine-5=-phosphosulfate (PAPS) as sulfate donor and are involved in a wide variety of biological processes such as cell communication, growth, development, defense, and detoxification (6,19,43,63,65). Unlike mammals, bacterial sulfotransferases are periplasmic enzymes that require phenolic sulfate esters as donor substrates, and it has been suggested that the intestinal microflora uses this enzyme to detoxify phenolic compounds (31,32,34,35).In Salmonella enterica serovar Typhi, the assT gene is located upstream of dsbL and dsbI, a couple of genes encoding a reduction-oxidation (red-ox) pair of proteins involved in the disulfide bond formation required for AssT activation in the periplasm (25,40,44). The nomenclature was adopted from the orthologous genes previously described in uropathogenic Escherichia coli (UPEC) and Salmonella enterica serovar Typhimurium (25,40).…”

“…In Salmonella enterica serovar Typhi, the assT gene is located upstream of dsbL and dsbI, a couple of genes encoding a reduction-oxidation (red-ox) pair of proteins involved in the disulfide bond formation required for AssT activation in the periplasm (25,40,44). The nomenclature was adopted from the orthologous genes previously described in uropathogenic Escherichia coli (UPEC) and Salmonella enterica serovar Typhimurium (25,40).…”

“…The nomenclature was adopted from the orthologous genes previously described in uropathogenic Escherichia coli (UPEC) and Salmonella enterica serovar Typhimurium (25,40). In contrast to the highly conserved assT, the genomic organization of the assT-dsbL-dsbI gene cluster is only conserved in Enterobacter, Yersinia, Citrobacter, and Escherichia strains, as well as within the Salmonella genus (5,12,25,40,41,62).…”