Identification of shuA, the gene encoding the heme receptor of Shigella dysenteriae, and analysis of invasion and intracellular multiplication of a shuA mutant

shuA encodes a 70-kDa outer membrane heme receptor in Shigella dysenteriae. Analysis of the shuA DNA sequence indicates that this gene encodes a protein with homology to TonB-dependent receptors of gram-negative bacteria. Transport of heme by the ShuA protein requires TonB and its accessory proteins ExbB and ExbD. The shuA DNA sequence contains a putative Fur box overlapping the -10 region of a potential shuA promoter, and the expression of shuA is repressed by exogenous iron or hemin in a Fur-dependent manner, although hemin repressed expression to a lesser extent than iron salts. Disruption of this open reading frame on the S. dysenteriae chromosome by marker exchange yielded a strain that failed to use heme as an iron source, indicating that shuA is essential for heme transport in S. dysenteriae. However, shuA is not essential for invasion or multiplication within cultured Henle cells; the shuA mutant invaded and produced normal plaques in confluent cell monolayers.