title: Key role for DsbA in cell-to-cell spread of Shigella flexneri, permitting secretion of Ipa proteins into interepithelial protrusions.
abstract: DsbA, a disulfide bond catalyst, is necessary for realization of the pathogenic potential of Shigella flexneri. Sh42, a mutant strain differing from wild-type M90TS solely because it expresses nonfunctional DsbA33G (substitution for 33C at the active site), secreted less IpaB and IpaC than M90TS in response to various stimuli in vitro. A kinetic study demonstrated that Sh42 responded more slowly to Congo red than M90TS. By modulating relative concentrations of functional and nonfunctional DsbA within bacteria, functional enzyme has been shown to be necessary for intercellular spread. By confocal microscopy, M90TS dividing in protrusions was shown to secrete Ipa proteins from the septation furrow, anticipating lysis of protrusions, while Sh42 showed minimal Ipa secretion in this location. In the light of a previous demonstration that DsbA is not necessary for entry of epithelial cells, we conclude that a role in virulence of this disulfide bond catalyst lies in facilitating secretion of Ipa proteins specifically within epithelial protrusions, in turn allowing cell-to-cell spread of S. flexneri.
authors.affiliation: Molecular Infectious Diseases Group, Department of Paediatrics, Imperial College School of Medicine, St. Mary's Campus, London W2 1PG, United Kingdom. jun.yu@ic.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: B
authors.initials: B
authors.lastname: Edwards-Jones
authors.forename: O
authors.initials: O
authors.lastname: Neyrolles
authors.forename: J S
authors.initials: JS
authors.lastname: Kroll
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D018938:Caco-2 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D019704:Protein Disulfide-Isomerases / Q000502:physiology*; D011817:Rabbits; D012763:Shigella flexneri / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; C087447:ipaB protein, Shigella; D019704:Protein Disulfide-Isomerases