title: Shigella chromosomal IpaH proteins are secreted via the type III secretion system and act as effectors.
abstract: Shigella possess 220 kb plasmid, and the major virulence determinants, called effectors, and the type III secretion system (TTSS) are exclusively encoded by the plasmid. The genome sequences of S. flexneri strains indicate that several ipaH family genes are located on both the plasmid and the chromosome, but whether their chromosomal IpaH cognates can be secreted from Shigella remains unknown. Here we report that S. flexneri strain, YSH6000 encodes seven ipaH cognate genes on the chromosome and that the IpaH proteins are secreted via the TTSS. The secretion kinetics of IpaH proteins by bacteria, however, showed delay compared with those of IpaB, IpaC and IpaD. Expression of the each mRNA of ipaH in Shigella was increased after bacterial entry into epithelial cells, and the IpaH proteins were secreted by intracellular bacteria. Although individual chromosomal ipaH deletion mutants showed no appreciable changes in the pathogenesis in a mouse pulmonary infection model, the DeltaipaH-null mutant, whose chromosome lacks all ipaH genes, was attenuated to mice lethality. Indeed, the histological examination for mouse lungs infected with the DeltaipaH-null showed a greater inflammatory response than induced by wild-type Shigella, suggesting that the chromosomal IpaH proteins act synergistically as effectors to modulate the host inflammatory responses.
authors.affiliation: Department of Microbiology and Immunology, International Research Center for Infectious Disease, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Tokyo 108-8639, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ashida
authors.forename: Takahito
authors.initials: T
authors.lastname: Toyotome
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagai
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D002876:Chromosomes, Bacterial / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D012763:Shigella flexneri / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C063500:ipaH protein, Shigella flexneri