IDENTIFICATION OF A PATHOGENICITY ISLAND REQUIRED FOR SALMONELLA ENTEROPATHOGENICITY

Salmonella spp. interact with ileal mucosa and disrupt normal intestin al function, which results in an acute inflammatory cell influx, fluid secretion and enteritis, We have recently characterized SopB, a novel secreted effector protein of Salmonella dublin, and presented evidenc e that SopB is translocated into eukaryotic cells via a sip-dependent pathway to promote fluid secretion and inflammatory responses. Here, w e show that sopB is located on a large DNA fragment unique to the Salm onella chromosome. This locus is conserved in Salmonella and maps at a pproximately 20 centisome of the S. typhimurium chromosome. Sequence a nalysis revealed that this Salmonella-specific DNA fragment is flanked by DNA sequences with significant sequence similarity to the Escheric hia coil K-12 genes, tRNA(1)(Ser) (serT) on one side and copS/copR on the other, Thus, this Salmonella-specific DNA fragment has features ch aracteristic of 'pathogenicity islands' and, therefore, it was denoted SPI-5 (Salmonella pathogenicity island-5). SPI-5 was sequenced and wa s found to contain five novel genes, pipA, pipB, pipC, pipD (pathogeni city island-encoded proteins) and orfX, in addition to sopB. The effec t of mutations in pipA, pipB and pipD on the induction of fluid secret ion and an acute inflammatory cell influx was assessed in bovine ligat ed ileal loops. The effect of mutations in SPI-5-encoded genes on syst emic salmonellosis was assessed in mice. The results of these experime nts suggest that SPI-5-encoded genes contribute to enteric but not to systemic salmonellosis.