The flagellar sigma factor fliA (sigma(28)) regulates the expression of Salmonella genes associated with the centisome 63 type III secretion system

One of the essential features of all pathogenic strains of Salmonella enter ica is the ability to enter into nonphagocytic cells. This pathogenic prope rty is mediated by the Salmonella pathogenicity island 1 (SPI-1)-encoded ty pe III secretion system. Expression of components and substrates of this sy stem is subject to complex regulatory mechanisms. These mechanisms include a number of specific and global transcriptional regulatory proteins. In thi s study we have compared in S. enterica serovars Typhimurium and Typhi the effect of mutations in flagellar genes on the phenotypes associated with th e SPI-1 type III protein secretion system. We found that serovar Typhi stra ins carrying a null mutation in either of the flagellar regulatory genes fl hDC or fliA were severely deficient in entry into cultured epithelial cells and macrophage cytotoxicity. This defect could not be reversed by applying a mild centrifugal force, suggesting that the effects of the mutations wer e not due to the absence of motility. In contrast, the same mutations had n o significant effect on the ability of serovar Typhimurium to enter into cu ltured Henle-407 cells or to induce macrophage cell death. Consistent with these observations, we found that the mutations in the flagellar regulatory proteins significantly reduced the expression of components of the SPI-1-e ncoded type III system in serovar Typhi but had a marginal effect in serova r Typhimurium. Our results therefore indicate that there is an overlap betw een regulatory mechanisms that control flagellar and type III secretion gen e expression in Salmonella serovar Typhi.