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Infection and Immunity, November 2000, p. 6449-6456, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Key Role for DsbA in Cell-to-Cell Spread of Shigella flexneri, Permitting Secretion of Ipa Proteins into Interepithelial Protrusions

Jun Yu,^1,* Bryn Edwards-Jones,¹ Olivier Neyrolles,^2, and J. Simon Kroll¹

Molecular Infectious Diseases Group, Department of Paediatrics,¹ and Department of Medical Microbiology,² Imperial College School of Medicine, St. Mary's Campus, London W2 1PG, United Kingdom

Received 5 July 2000/Returned for modification 9 August 2000/Accepted 18 August 2000

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.

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^* Corresponding author. Mailing address: Molecular Infectious Diseases Group, Department of Paediatrics, Imperial College School of Medicine, St. Mary's Campus, London W2 1PG, United Kingdom. Phone: (44) 20 7886 6340. Fax: (44) 20 7886 6284. E-mail: jun.yu{at}ic.ac.uk.

Present address: Service de Microbiologie, Hôpital Saint Louis, 75475 Paris Cedex 10, France.

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Infection and Immunity, November 2000, p. 6449-6456, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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