MUTATIONS IN SALMONELLA PATHOGENICITY ISLAND-2 (SP12) GENES AFFECTINGTRANSCRIPTION OF SPI1 GENES AND RESISTANCE TO ANTIMICROBIAL AGENTS

The Salmonella typhimurium genome contains two pathogenicity islands ( SPI) with genes encoding type III secretion systems for virulence prot eins. SPI1 is required for the penetration of the epithelial layer of the intestine. SPI2 is important for the subsequent proliferation of b acteria in the spleens of infected hosts. Although most mutations in S PI2 lead to a strong reduction of virulence, they have different effec ts in vitro, with some mutants having significantly increased sensitiv ity to gentamicin and the antibacterial peptide polymyxin B. Previousl y we showed that certain mutations in SPI2 affect the ability of S. ty phimurium to secrete SPI1 effector proteins and to invade cultured euk aryotic cells. In this study,,ve show that these SPI2 mutations affect the expression of the SPI1 invasion genes. Analysis of reporter fusio ns to various SPI1 genes reveals highly reduced expression of sipC, pr gK, and hilA, the transcriptional activator of SPI1 genes. These obser vations indicate that the expression of one type III secretion system can be influenced dramatically by mutations in genes encoding a second type III secretion system in the same cell.