A flagellar gene fliZ regulates the expression of invasion genes and virulence phenotype in Salmonella enterica serovar Typhimurium

We previously reported that the fliZ gene encodes a positive regulatory factor for the class 2 flagellar operons in Salmonella enterica serovar Typhimurium. In this study, we found that the fliZ mutation reduced not only the amounts of excreted flagellar proteins, but also those of several secreted invasion proteins encoded by the genes within Salmonella pathogenicity island 1. Using the lacZ gene fused to a subset of virulence-associated genes, we show that this downregulation was caused by a decreased transcription of the hilA gene, which encodes a positive regulator for the invasion genes. We further show that the fliZ mutation reduced invasion ability of S. enterica serovar Typhimurium to HEp-2 cells. Consistent with these results, orally challenged cells of the fliZ mutant show an attenuated virulence phenotype in a mouse typhoid model. These results indicate that the fliZ gene product positively regulates the invasion genes and is necessary for expression of full virulence.