Global regulation by CsrA in Salmonella typhimurium

Abstract

SummaryCsrA is a regulator of invasion genes in Salmonella enterica serovar Typhimurium. To investigate the wider role of CsrA in gene regulation, we compared the expression of Salmonella genes in a csrA mutant with those in the wild type using a DNA microarray. As expected, we found that expression of Salmonella pathogenicity island 1 (SPI-1) invasion genes was greatly reduced in the csrA mutant, as were genes outside the island that encode proteins translocated into eukaryotic cells by the SPI-1 type III secretion apparatus. The flagellar synthesis operons, flg and fli , were also poorly expressed, and the csrA mutant was aflagellate and non-motile. The genes of two metabolic pathways likely to be used by Salmonella in the intestinal milieu also showed reduced expression: the pdu operon for utilization of 1,2-propanediol and the eut operon for ethanolamine catabolism. Reduced expression of reporter fusions in these two operons confirmed the microarray data. Moreover, csrA was found to regulate co-ordinately the cob operon for synthesis of vitamin B 12 , required for the metabolism of either 1,2-propanediol or ethanolamine. Additionally, the csrA mutant poorly expressed the genes of the mal operon, required for transport and use of maltose and maltodextrins, and had reduced amounts of maltoporin, normally a dominant protein of the outer membrane. These results show that csrA controls a number of gene classes in addition to those required for invasion, some of them unique to Salmonella , and suggests a co-ordinated bacterial response to conditions that exist at the site of bacterial invasion, the intestinal tract of a host animal.

Examination of animal and zoonotic pathogens using microarrays

“…The study demonstrated alterations in global regulator, PNPase as a key element of virulence and persistency of Salmonella. The role of another global regulator, csrA in virulence of S. enterica Typhimurium was found in a similar study [59]. Recent analyses of gene expression of double murein lipoprotein mutant of the pathogen revealed alterations in the expression of flagellar, invasion, and virulence gene regulators in the mutant compared to the parent strain.…”

Overexpression of CsrA (BB0184) Alters the Morphology and Antigen Profiles ofBorrelia burgdorferi

“…Since the effects of CsrA homologs in other eubacterial species have been shown to be antagonized via interactions with multiple binding sites present on noncoding small RNA molecules such as CsrB and CsrC, we hypothesized that the effects of CsrA in borrelial strains could be subjected to such regulatory effects by small RNA homologs (6,46). Bioinformatic approaches to identify the small RNA molecule(s) that could titrate the effects of CsrA have not yielded sequences with significant homology to CsrB/CsrC, while a homolog of small RNA molecule DsrA Bb has been determined to mediate the temperature-induced regulation of RpoS (50).…”

FliW antagonizes CsrA RNA binding by a noncompetitive allosteric mechanism

“…Mutation of CsrA in these organisms has dramatic and highly pleiotropic defects in carbon metabolism, quorum sensing, biofilm formation, and motility (17)(18)(19)(20). CsrA-deficient bacterial pathogens are typically attenuated for virulence, which is likely a result of misregulation of target gene expression and the resulting inability to make critical physiological transitions during an infection (1,(21)(22)(23).…”