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: In our previous report, we used an experimental system in which cultured HSAECs were infected with B. anthracis spores and the responses of the cells to the germinating spores and vegetative bacteria were studied (Popova et al., 2009). The results indicated that during the first 8 h of incubation, bacteria of the toxigenic Sterne strain 34F2 growing in the culture medium on top of the confluent HSAECs under static conditions at 37 °C and 5% CO2 did not influence HSAEC viability, although during this period of time, bacteria secreted more than 3 μg mL−1 of LeTx and EdTx. In the current study, we found that longer incubation times resulted in a progressive loss of HSAEC viability and wanted to elucidate the nature of this toxic effect. Analysis of the bacterial cultures grown in the absence of HSAECs revealed that the toxicity resided in the supernatant fraction (Sup). The results in Fig. 1a show that Sups of the 24-h cultures grown under the conditions of the experiments with HSAECs demonstrated a high level of toxicity when HSAECs were exposed to Sups for 2 h. The pelleted and washed bacteria resuspended in the original volume of fresh culture medium had no toxicity (not shown), indicating that toxicity was due to the activity of secreted bacterial factors.
Affiliation: National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, USA.