IpaB mediates macrophage apoptosis induced by Shigella flexneri.

Abstract:

:Shigella flexneri kills macrophages through apoptosis, involving the induction of host cell DNA fragmentation and characteristic morphological changes. Shigella can only cause damage if it escapes from the phagolysosome into the cytoplasm. The S. flexneri cytotoxic genes have been localized to the ipa operon of shigella's virulence plasmid. ipaB, C and D deletion mutants are not invasive and therefore not cytotoxic. In order to distinguish genes involved in the escape from the phagolysosome as distinct from cytotoxicity, we constructed Shigella strains that secrete low amounts of Escherichia coli haemolysin (hly(low)). These strains can escape into the cytoplasm of the macrophage even in the absence of the invasion plasmid as verified by electron microscopy and resistance to chloroquine. Macrophages were infected with different ipa mutants expressing hly(low). Both delta ipaC hly(low) and delta ipaD hly(low) were cytotoxic whilst delta ipaB hly(low) and a hly(low) strain cured of shigella's pathogenicity plasmid were not. Furthermore, both delta ipaC hly(low) and delta ipaD hly(low) killed through apoptosis as shown by both changes in ultrastructural morphology and fragmentation of the host cell DNA. These results demonstrate that ipaB is essential for S. flexneri to induce apoptosis in macrophages.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Zychlinsky A,Kenny B,Ménard R,Prévost MC,Holland IB,Sansonetti PJ

doi

10.1111/j.1365-2958.1994.tb00341.x

subject

Has Abstract

pub_date

1994-02-01 00:00:00

pages

619-27

issue

4

eissn

0950-382X

issn

1365-2958

journal_volume

11

pub_type

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