INDUCTION OF TYPE-III SECRETION IN SHIGELLA-FLEXNERI IS ASSOCIATED WITH DIFFERENTIAL CONTROL OF TRANSCRIPTION OF GENES ENCODING SECRETED PROTEINS

Shigella, the etiological agent of human bacillary dysentery, invades the colonic epithelium where it induces an intense inflammatory respon se. Entry of Shigella into epithelial cells involves a type III secret ion machinery, encoded by the mxi and spa operons, and the IpaA-D secr eted proteins. In this study, we have identified secreted proteins of 46 and 60 kDa as the products of virA and ipaH9.8, respectively, the l atter being a member of the ipaH multigene family. Inactivation of vir A did not affect entry into epithelial cells. Using lacZ transcription al fusions, we found that transcription of virA and four ipaH genes, b ut not that of the ipaBCDA and mxi operons, was markedly increased dur ing growth in the presence of Congo red and in an ipaD mutant, two con ditions in which secretion through the Mxi-Spa machinery is enhanced. Transcription of the virA and ipaH genes was also transiently activate d upon entry into epithelial cells. These results suggest that transcr iption of the virA and ipaH genes is regulated by the type III secreti on machinery and that a regulatory cascade differentially controls tra nscription of genes encoding secreted proteins, some of which, like vi rA, are not required for entry.