Regulation of igaA and the Rcs System by the MviA Response Regulator in Salmonella enterica

IgaA is a membrane protein that prevents overactivation of the Rcs regulatory system in enteric bacteria. Here we provide evidence that igaA is the first gene in a 70-dependent operon of Salmonella enterica serovar Typhimurium that also includes yrfG, yrfH, and yrfI. We also show that the Lon protease and the MviA response regulator participate in regulation of the igaA operon. Our results indicate that MviA regulates igaA transcription in an RpoS-dependent manner, but the results also suggest that MviA may regulate RcsB activation in an RpoS- and IgaA-independent manner. In Salmonella enterica serovar Typhimurium, the igaA gene is located at centisome 75, between genes yrfE and yrfG (60). igaA encodes an inner membrane protein of 710 amino acids which is predicted to contain five transmembrane domains (28). igaA is homologous to yrfF in Escherichia coli and umoB in Proteus mirabilis (29) and was identified by analysis of a mutant with an increased growth rate in fibroblasts (16). This mutant harbored a substitution mutation, and the resulting allele was designated igaA1 (16). Mutants in the same gene (also named mucM) were independently isolated on the basis of their resistance to amdinocillin (23). igaA1 and other igaA point mutants are mucoid (due to upregulation of the wca genes), show a defect in motility (due to repression of the flhDC operon), and are attenuated for virulence (16). The attenuation is not explained by the motility defect but is par-tially explained by the overproduction of colanic acid capsule (28, 40). Different mucoid igaA point mutants display similar phenotypes but in different degrees that correlate with the degree of activation of the Rcs system (28). igaA is an essential gene (15). The phenotypes of viable (leaky) igaA point mutants and the lethality of null alleles are suppressed by mutations i