Researchers at the Stanford School of Medicine recently found that individuals have varying levels of susceptibility to anthrax toxins due to inherited genetic traits.
The study, which was published online Monday in the Proceedings of the National Academy of Sciences, discussed possible national security implications and noted how the findings could extend beyond anthrax toxins to apply to other pathogens, such as HIV, malaria, leprosy and hepatitis.
Researchers utilized the International HapMap Project — a multi-country initiative to catalog genes into a free, public resource — to obtain 234 samples of immune cells called lymphocytes. These samples belonged to individuals of diverse backgrounds, including 84 Nigerians, 63 Americans with a Northern or Western European ancestry, 44 Japanese and 43 Han Chinese. Researchers then introduced an engineered hybrid toxin into each of these samples of cells.
Samples from three individuals — who were of European ancestry — were completely resistant to the toxin. Others needed 250 times more exposure to the toxin to kill the same amount of cells as in another sample. Researchers later linked these discrepancies in toxin resistance to the level of expression of a gene that produces CMG2. CMG2 is a cell-surface protein that affects the anthrax toxin’s ability to enter into human cells.
Before this study, whether differences in the effects of exposure to anthrax toxins were due to genetic or environmental factors remained uncertain.
“This is one of the few studies that has successfully identified a host-genetics-based molecular cause of this variability,” said David Relman, medical professor and the chair of the Institute of Medicine’s Forum on Microbial Threats, in a School of Medicine press release. Relman was not associated with the research.
The study suggests that individuals who are more resistant to anthrax could be the ideal “first-line responders” in the event of a national security crisis that involves exposure to the toxin. Researchers noted other possible implications.
“Our findings, which reveal the previously unsuspected magnitude of genetically determined differences in toxin sensitivity among cells from different individuals, suggest a broadly applicable approach for investigating pathogen susceptibility in diverse human populations,” the authors noted in the study.
School of Medicine professor Stanley Cohen was the senior author of the report, and postdoctoral scholar Mikhail Martchenko was the first author. Associate professor of genetics Hua Tang and research associate Sophie Candille also contributed to the study.
— Kurt Chirbas