1887

Abstract

The alternative sigma factor () is essential for survival of Typhimurium but is dispensable during growth in the laboratory. We have been identifying -regulated genes and studying their regulation and function to elucidate their potential role in the severe attenuation of Typhimurium mutants. In this study we identify five promoters that control the , (), region. A confirmed -dependent promoter, , and a second downstream promoter, , are located within the upstream gene and direct expression of the downstream genes. The only known function of RseP is activation, and it is therefore not expected to be essential for . Typhimurium . However, it proved impossible to delete the entire gene due to the presence of internal promoters that regulate the essential gene . We could inactivate by deleting the first third of the gene, leaving the promoters intact. Like the mutant, the mutant exhibited severe attenuation . We were able to delete the entire coding sequence of , which encodes a periplasmic chaperone involved in targeting misfolded outer-membrane proteins to the -barrel assembly machinery. The mutant was attenuated in mice after oral and parenteral infection. Virulence could be complemented by providing but only by linking it to a heterologous -regulated promoter. The reason the mutant is attenuated is currently enigmatic, but we know it is not through increased sensitivity to a variety of RpoE-activating host stresses, such as HO, polymyxin B and high temperature, or through altered secretion of effector proteins by either the pathogenicity island (SPI)-1 or the SPI-2 type III secretion system.

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2011-03-01
2019-12-11
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