Anthrolysin O and fermentation products mediate the toxicity of Bacillus anthracis to lung epithelial cells under microaerobic conditions.
Bottom Line: Human small airway epithelial, umbilical vein endothelial, Caco-2, and Hep-G2 cells were found to be susceptible.Its effect was found to be synergistic with a metabolic product of B. anthracis, succinic acid.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.
Affiliation: National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, USA.Show MeSH
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Mentions: Comparison of Sups generated in different media showed that the highest toxicity was detected in the case of bacteria grown in the CSFM medium, in contrast to DMEM/F-12 and Luria broth (Fig. 2a, lower panels). We noticed that CSFM contains a high amount of nitrate (∼300 μM in CSFM vs. <1 μM in DMEM/F-12) and suggested that it may play a role in toxicity through changes in bacterial metabolism. Nitrate is known to replace oxygen for bacterial respiration under microaerobic (reduced oxygen) conditions present in static bacterial cultures (Hassett, 1996; Wyckoff et al., 2002; Ju et al., 2005; Pettersen et al., 2005;). The resulting process of denitrification (Ju et al., 2005; Rock et al., 2005;) can lead to the consumption of nitrate. Indeed, microaerobic cultivation of B. anthracis in CSFM under static conditions was accompanied by a reduction in the nitrate content (Fig. 2b) and acidification of the medium to pH 5.3–5.5 (Fig. 2a, middle panels), indicating anaerobic acid fermentation.
Affiliation: National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, USA.