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IpaB mediates macrophage apoptosis induced by Shigella flexneri
Author(s) -
Zychlinsky Arturo,
Kenny Brendan,
Ménard Robert,
Prévost MarieChristine,
Holland I. Barry,
Sansonetti Philippe J.
Publication year - 1994
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.1994.tb00341.x
Subject(s) - shigella flexneri , phagolysosome , biology , shigella , microbiology and biotechnology , cytotoxic t cell , plasmid , mutant , virulence , gene , phagocytosis , escherichia coli , phagosome , genetics , in vitro
Summary 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 δipaC hly low and δipaD hly low were cytotoxic whilst δipaB hly low and a hly low strain cured of shigella's pathogenicity plasmid were not. Furthermore, both δipC ahly low and δipaD hly low killed through apoptosis as shown by both changes in ultrastructural morphology and fragmentation of the host ceil DNA. These results demonstrate that ipaB is essential for S. flexneri to induce apoptosis in macrophages.