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Published on: September 2, 2014
Induction of macrophage apoptosis by Bordetella pertussis adenylate cyclase-hemolysin
Abstract:
We previously demonstrated that Bordetella pertussis induced macrophage apoptosis and that adenylate cyclase-hemolysin expression is required for this phenomenon. In order to determine a role for other B. pertussis factors, such as pertussis toxin or the adhesins, pertactin and filamentous hemagglutinin, we compared mutants deficient in adhesin expression or purified proteins for their ability to induce cell death. We showed that only purified adenylate cyclase-hemolysin, but neither adhesins, nor pertussis toxin, killed macrophages through apoptosis. We also demonstrated that all activities of adenylate cyclase-hemolysin were required. Moreover, our results indicate that B. pertussis does not have to invade cells to be lethal.
Insights
Bordetella pertussis causes macrophage apoptosis primarily through its adenylate cyclase-hemolysin toxin. Other virulence factors like pertussis toxin and adhesins are not responsible for this cell death.
Area of Science:
- Bacteriology
- Immunology
- Cell Biology
Background:
- Bordetella pertussis is known to induce apoptosis in macrophages.
- Adenylate cyclase-hemolysin (ACH) expression is essential for this observed apoptosis.
- The roles of other B. pertussis virulence factors in apoptosis were not fully elucidated.
Purpose of the Study:
- To investigate the specific B. pertussis factors responsible for inducing macrophage apoptosis.
- To determine if pertussis toxin, pertactin, or filamentous hemagglutinin contribute to cell death.
- To confirm the necessity of adenylate cyclase-hemolysin's activities for apoptosis induction.
Main Methods:
- Comparison of B. pertussis mutants deficient in specific virulence factors.
- Assessment of purified adenylate cyclase-hemolysin, pertussis toxin, and adhesins for their ability to induce apoptosis.
- Evaluation of the requirement for all adenylate cyclase-hemolysin activities in cell death.
Main Results:
- Only purified adenylate cyclase-hemolysin induced macrophage apoptosis.
- Pertussis toxin, pertactin, and filamentous hemagglutinin did not induce apoptosis.
- All activities of adenylate cyclase-hemolysin were necessary for inducing apoptosis.
- B. pertussis does not require cell invasion to cause lethality.
Conclusions:
- Adenylate cyclase-hemolysin is the sole B. pertussis factor responsible for inducing macrophage apoptosis.
- B. pertussis virulence and lethality can occur independently of intracellular invasion.
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