title: Haemolysin II is a Bacillus cereus virulence factor that induces apoptosis of macrophages.
abstract: Bacillus cereus is a Gram-positive spore-forming bacterium causing food poisoning and serious opportunistic infections. These infections are characterized by bacterial accumulation despite the recruitment of phagocytic cells. The precise mechanisms and the bacterial factors allowing B. cereus to circumvent host immune responses remain to be elucidated. We have previously shown that B. cereus induces macrophage cell death by an unknown mechanism. Here we identified the toxic component from the B. cereus supernatant. We report that Haemolysin II (HlyII) provokes macrophage cell death by apoptosis through its pore-forming activity. The HlyII-induced apoptotic pathway is caspase 3 and 8 dependent, thus most likely mediated by the death receptor pathway. Using insects and mice as in vivo models, we show that deletion of hlyII strongly reduces virulence. In addition, we show that after infection of Bombyx mori larvae, the immune cells are apoptotic, demonstrating that HlyII induces apoptosis of phagocytic cells in vivo. Altogether, our results clearly unravel HlyII as a novel virulence protein that induces apoptosis in phagocytic cells in vitro and in vivo.
authors: INRA, Unité MICALIS, UMR 1319, équipe GME, La Minière, 78285 Guyancourt, France.
authors: Seav-Ly
authors: SL
authors: Tran
authors: Elisabeth
authors: E
authors: Guillemet
authors: Maud
authors: M
authors: Ngo-Camus
authors: Cyril
authors: C
authors: Clybouw
authors: Andrea
authors: A
authors: Puhar
authors: Arnaud
authors: A
authors: Moris
authors: Michel
authors: M
authors: Gohar
authors: Didier
authors: D
authors: Lereclus
authors: Nalini
authors: N
authors: Ramarao
mesh_terms: D000818:Animals; D017209:Apoptosis; D001409:Bacillus cereus / Q000235:genetics / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity*; D012831:Bombyx; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D017353:Gene Deletion; D006460:Hemolysin Proteins / Q000235:genetics / Q000633:toxicity*; D006801:Humans; D007814:Larva / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000633:toxicity*
chemical_list: C085361:ApxII toxin, bacteria; D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D037521:Virulence Factors; D053148:Caspase 3; D053181:Caspase 8