Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions
Abstract
Bacillus anthracis generates virulence factors such as lethal and edema toxins, capsule, and hemolytic proteins under conditions of reduced oxygenation. Here, we report on the acute cytotoxicity of culture supernatants (Sups) of six nonencapsulated B. anthracis strains grown till the stationary phase under static microaerobic conditions. Human small airway epithelial, umbilical vein endothelial, Caco-2, and Hep-G2 cells were found to be susceptible. Sups displayed a reduction of pH to 5.3–5.5, indicating the onset of acid anaerobic fermentation; however, low pH itself was not a major factor of toxicity. The pore-forming hemolysin, anthrolysin O (ALO), contributed to the toxicity in a concentrationdependent manner. Its effect was found to be synergistic with a metabolic product of B. anthracis, succinic acid. Cells exposed to Sups demonstrated cytoplasmic membrane blebbing, increased permeability, loss of ATP, mitochondrial membrane potential collapse, and arrest of cell respiration. The toxicity was reduced by inhibition of ALO by cholesterol, decomposition of reactive oxygen species, and inhibition of mitochondrial succinate dehydrogenase. Cell death appears to be caused by an acute primary membrane permeabilization by ALO, followed by a burst of reactive radicals from the mitochondria fuelled by the succinate, which is generated by bacteria in the hypoxic environment. This mechanismmore »
- Authors:
-
- George Mason Univ., Fairfax, VA (United States). National Center for Biodefense and Infectious Diseases
- Publication Date:
- Research Org.:
- George Mason Univ., Fairfax, VA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA)
- OSTI Identifier:
- 1625902
- Grant/Contract Number:
- FC52-04NA25455
- Resource Type:
- Accepted Manuscript
- Journal Name:
- FEMS Immunology & Medical Microbiology
- Additional Journal Information:
- Journal Volume: 61; Journal Issue: 1; Journal ID: ISSN 0928-8244
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; immunology; infectious diseases; microbiology; pore-forming toxin; oxidative stress; anthrax; lung epithelium
Citation Formats
Popova, Taissia G., Millis, Bryan, Chung, Myung-Chul, Bailey, Charles, and Popov, Serguei G. Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions. United States: N. p., 2011.
Web. doi:10.1111/j.1574-695x.2010.00740.x.
Popova, Taissia G., Millis, Bryan, Chung, Myung-Chul, Bailey, Charles, & Popov, Serguei G. Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions. United States. https://doi.org/10.1111/j.1574-695x.2010.00740.x
Popova, Taissia G., Millis, Bryan, Chung, Myung-Chul, Bailey, Charles, and Popov, Serguei G. Fri .
"Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions". United States. https://doi.org/10.1111/j.1574-695x.2010.00740.x. https://www.osti.gov/servlets/purl/1625902.
@article{osti_1625902,
title = {Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions},
author = {Popova, Taissia G. and Millis, Bryan and Chung, Myung-Chul and Bailey, Charles and Popov, Serguei G.},
abstractNote = {Bacillus anthracis generates virulence factors such as lethal and edema toxins, capsule, and hemolytic proteins under conditions of reduced oxygenation. Here, we report on the acute cytotoxicity of culture supernatants (Sups) of six nonencapsulated B. anthracis strains grown till the stationary phase under static microaerobic conditions. Human small airway epithelial, umbilical vein endothelial, Caco-2, and Hep-G2 cells were found to be susceptible. Sups displayed a reduction of pH to 5.3–5.5, indicating the onset of acid anaerobic fermentation; however, low pH itself was not a major factor of toxicity. The pore-forming hemolysin, anthrolysin O (ALO), contributed to the toxicity in a concentrationdependent manner. Its effect was found to be synergistic with a metabolic product of B. anthracis, succinic acid. Cells exposed to Sups demonstrated cytoplasmic membrane blebbing, increased permeability, loss of ATP, mitochondrial membrane potential collapse, and arrest of cell respiration. The toxicity was reduced by inhibition of ALO by cholesterol, decomposition of reactive oxygen species, and inhibition of mitochondrial succinate dehydrogenase. Cell death appears to be caused by an acute primary membrane permeabilization by ALO, followed by a burst of reactive radicals from the mitochondria fuelled by the succinate, which is generated by bacteria in the hypoxic environment. This mechanism of metabolic toxicity is relevant to the late-stage conditions of hypoxia and acidosis found in anthrax patients and might operate at anatomical locations of the host deprived from oxygen supply},
doi = {10.1111/j.1574-695x.2010.00740.x},
journal = {FEMS Immunology & Medical Microbiology},
number = 1,
volume = 61,
place = {United States},
year = {Fri Feb 11 00:00:00 EST 2011},
month = {Fri Feb 11 00:00:00 EST 2011}
}
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