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Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
Published on: June 25, 2015
Haemolysin II is a Bacillus cereus virulence factor that induces apoptosis of macrophages
Seav-Ly Tran1, Elisabeth Guillemet, Maud Ngo-Camus
1INRA, Unité MICALIS, UMR 1319, équipe GME, La Minière, 78285 Guyancourt, France.
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.
Insights
Bacillus cereus uses Haemolysin II (HlyII) to induce apoptosis in immune cells, promoting bacterial infections. This discovery reveals HlyII as a key virulence factor in B. cereus pathogenesis.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Bacillus cereus causes food poisoning and opportunistic infections.
- B. cereus infections involve bacterial accumulation despite phagocyte presence.
- Mechanisms of immune evasion by B. cereus are not fully understood.
Purpose of the Study:
- Identify the toxic component in B. cereus supernatant responsible for macrophage cell death.
- Elucidate the role of bacterial factors in circumventing host immune responses.
Main Methods:
- Analysis of B. cereus supernatant to isolate toxic factors.
- Investigating the mechanism of macrophage cell death induced by purified toxins.
- Utilizing in vivo models (insects and mice) to assess bacterial virulence.
- Employing genetic deletion of specific genes (hlyII) to study virulence reduction.
Main Results:
- Haemolysin II (HlyII) was identified as the toxic component inducing macrophage apoptosis.
- HlyII induces apoptosis via pore-forming activity, dependent on caspase 3 and 8.
- Deletion of hlyII significantly reduced B. cereus virulence in vivo.
- Apoptosis of immune cells was observed in Bombyx mori larvae infected with B. cereus.
Conclusions:
- Haemolysin II (HlyII) is a novel virulence protein of Bacillus cereus.
- HlyII induces apoptosis in phagocytic cells both in vitro and in vivo.
- HlyII contributes significantly to B. cereus pathogenesis by targeting host immune cells.
Related Concept Videos
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Determinants of Bacterial Pathogenicity and Virulence
Caspases
Bacterial Toxins
Inhalation Anthrax
The Intrinsic Apoptotic Pathway

