Pseudomonas aeruginosa ExoT Induces Atypical Anoikis Apoptosis in Target Host Cells by Transforming Crk Adaptor Protein into a Cytotoxin

Previously, we demonstrated that Pseudomonas aeruginosa ExoT induces potent apoptosis in host epithelial cells in a manner that primarily depends on its ADP-ribosyltransferase domain (ADPRT) activity. However, the mechanism underlying ExoT/ADPRT-induced apoptosis remains undetermined. We now report that ExoT/ADPRT disrupts focal adhesion sites, activates p38β and JNK, and interferes with integrin-mediated survival signaling; causing atypical anoikis. We show that ExoT/ADPRT-induced anoikis is mediated by the Crk adaptor protein. We found that Crk^-/- knockout cells are significantly more resistant to ExoT-induced apoptosis, while Crk^-/- cells complemented with Crk are rendered sensitive to ExoT-induced apoptosis. Moreover, a dominant negative (DN) mutant form of Crk phenocopies ExoT-induced apoptosis both kinetically and mechanistically. Crk is generally believed to be a component of focal adhesion (FA) and its role in cellular survival remains controversial in that it has been found to be either pro-survival or pro-apoptosis. Our data demonstrate that although Crk is recruited to FA sites, its function is likely not required for FA assembly or for survival per se. However, when modified by ExoT or by mutagenesis, it can be transformed into a cytotoxin that induces anoikis by disrupting FA sites and interfering with integrin survival signaling. To our knowledge, this is the first example whereby a bacterial toxin exerts its cytotoxicity by subverting the function of an innocuous host cellular protein and turning it against the host cell.     

Wichtigere neue Funde von Phanerogamen in Nordtirol

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Recurrence of the unfit

Domination among strategies in an evolutionary game implies that the geometric mean of the frequencies of certain strategies—the unfit—approaches zero. However, as we show by example no one strategy need be eliminated in the limit.     

Über eigenartige organische Membraneinschlüsse in der Epidermis vonPortulaca Gilliesii Hook

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Gagea Szepusiana mihi

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Über den Hausschwamm und seine nächsten Verwandten

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Observations on the occurrence and maturation of the nematode Rhabdochona denudata (Dujardin, 1845) in Chub, Leuciscus cephalus (L.), of the Rokytná River, Czechoslovakia

From October 1985 until July 1987, the seasonal dynamics of Rhabdochona denudata in its principal definitive host, the chub (Leuciscus cephalus), was studied in the Rokytná River (the Danube basin), Czechoslovakia. Prevalence (overall prevalence 77%) and intensity of infection (1-59 nematodes per fish) in the fish were high all year, with both abiotic and biotic factors influencing the fluctuations. Maximum values of prevalence (82-87%) were found in the fish with body length exceeding 20 cm; the mean intensity was highest in the size-group of fish 20-25 cm long, whereas its values gradually decreased in larger fish, this being due to the choice of food by fish of different size-groups. In contrast to the situation in other localities, an annual maturation cycle was not evident and egg-producing female nematodes were present in fish throughout the year. New infections in fish were most common in summer but occurred all year round. This life history pattern seems to be mainly due to the availability of infected ephemeropteran intermediate hosts during all seasons, in this case the nymphs of Ephemera danica, a species noted for its two-year development. In this locality, specifically not determined Rhabdochona larvae were recorded from the mayfly nymphs Ephemera danica (0.4%), Ecdyonurus aurantiacus (7%), and Caenis macrura (10%). The diet of the chub included mayfly nymphs at all seasons.     

Beitrag zur Kenntnis der Flora von West-Bosnien

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