title: Shigella flexneri cell-to-cell spread, and growth and inflammation in mice, is limited by the outer membrane protease IcsP.
abstract: The Shigella flexneri autotransporter protein IcsA is essential for intra- and intercellular spread, and icsA mutants are attenuated in several models. However, the pathogenic significance of the outer membrane protease IcsP, which orchestrates the polar distribution of IcsA on the bacterial surface, remains unclear. To further examine this point, we constructed icsP mutants in the two most commonly studied S. flexneri strains and evaluated their in vitro and in vivo performance relative to wild type. Both icsP mutants showed aberrant surface distribution of IcsA, but the in vitro consequences depended upon the cell line being used to assess bacterial motility and plaque formation. Evaluating the behaviour of the mutants in two mouse models suggested functional expression of icsP might limit bacterial persistence and the associated inflammation in host tissues, consistent with the findings in one of the three cell lines used.
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Elizabeth Ngoc Hoa
authors.initials: EN
authors.lastname: Tran
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Attridge
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Min Yan
authors.initials: MY
authors.lastname: Teh
authors.affiliation: Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia renato.morona@adelaide.edu.au.
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
mesh_terms: D000199:Actins / Q000235:genetics; D000617:Aminoglycosides; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012763:Shigella flexneri / Q000235:genetics* / Q000472:pathogenicity*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000199:Actins; D000617:Aminoglycosides; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C058483:virG protein, Shigella flexneri; C053067:1,2-diamino-1,2-N,N'-carbonyl-1,2-dideoxyglucose hydrate; C060971:SopA protein, Bacteria
keywords: Shigella flexneri; bacterial virulence; cell-to-cell spread; mice inflammation; protease