Haemolysin II is a Bacillus cereus virulence factor that induces apoptosis of macrophages

Seav-Ly Tran, Elisabeth Guillemet, Maud Ngo-Camus, Cyril Clybouw, Andrea Puhar, Arnaud Moris, Michel Gohar, Didier Lereclus, Nalini Ramarao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)92-108
Number of pages17
JournalCellular Microbiology
Volume13
Issue number1
Early online date23 Aug 2010
DOIs
Publication statusPublished - Jan 2011
Externally publishedYes

Bibliographical note

© 2010 Blackwell Publishing Ltd.

Keywords

  • Animals
  • Apoptosis
  • Bacillus cereus/genetics
  • Bacterial Proteins/genetics
  • Bombyx
  • Caspase 3/metabolism
  • Caspase 8/metabolism
  • Cell Line
  • Cell Survival/drug effects
  • Female
  • Gene Deletion
  • Hemolysin Proteins/genetics
  • Humans
  • Larva/microbiology
  • Macrophages/microbiology
  • Mice
  • Mice, Inbred C57BL
  • Survival Analysis
  • Virulence
  • Virulence Factors/genetics

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