Millions of cases of shigellosis, caused by the Shigella species, are reported annually. Shigella spp. must acquire all essential nutrients, including iron (Fe), to survive and cause disease within the human host. The presence of Fe within the microenvironment influences the expression of genes whose products are required for Fe acquisition by Shigella (Mills and Payne, 1995; Mills and Payne, 1997). The mechanisms governing Fe regulated gene expression are not fully understood. This proposal aims to characterize the mechanisms controlling the Fe influenced expression of shuA, a gene encoding an outer membrane heme receptor whose function is essential for the utilization of heme as a source of nutrient Fe by S. dysenteriae.
The specific aims set forth in this proposal are to: 1) characterize the promoter controlling expression of S. dysenteriae shuA; 2) investigate the mechanisms controlling the Fe-regulated expression of shuA; and 3) analyze the influence of heme on the expression of shuA. A complete understanding of Fe acquisition, including the genes and proteins involved, will lead to a fuller appreciation of the strategies employed by Shigella spp. for survival and proliferation within the human host.
