Understanding anthrax and how it can persist in our lungs

Understanding anthrax: How it can evade the immune system

Texas A&M researchers work to better understand how this wily bacterium can persist in our lungs…and what we can do to stop it
August 22, 2016

Anthrax is a stubborn disease that has likely plagued us since ancient times. The bacteria’s ability to form spores that can survive, dormant, for years before infecting its next host makes it very difficult to combat. Even with aggressive treatment, about 45 percent of those infected with inhaled anthrax do not survive.

Now, according to research published recently in the journal PLoS Pathogens, researchers at the Texas A&M Institute of Biosciences & Technology have found one way anthrax spores can evade the immune system. They hope this knowledge will aid in the development of more effective vaccines and treatments.

Yi Xu, PhD, associate professor at the Center for Infectious and Inflammatory Diseases and author of the study, began working on Bacillus anthracis, the pathogen that causes anthrax, when she was a postdoctoral fellow in 2001. “It was around the same time as the anthrax letters,” she said. “I wanted to apply the knowledge I had to find a way to combat this organism.”

Spores are extremely hardy and resistant to most types of antimicrobials. When anthrax spores are inhaled, they lodge in the epithelial cells of the lung’s lining, where they can persist for weeks or even months. “We started looking at mechanisms that would allow spores to persist,” Xu said. “We found that there is a protein on the surface of the spore that recruits a component of the host’s innate immune system.” This interaction engages a regulator called factor H, which modulates the activation of the complement system—the part of the immune system that is a first line of defense again invading pathogens.

“If the spores get into the lungs, the complement system is one of the first things they will encounter,” Xu said. B. anthracis spores have adopted a strategy to downregulate the activation of the complement system: essentially, convince the host’s body that the threat is over and there is no need to react. Such signals are important because they allow spores to avert clearance by the host immune system and survive.

READ MORE: What has anthrax taught us about public health preparedness?

“It’s interesting that the anthrax microbes recruit this negative regulator to their own advantage,” Xu said. “It’s trying to protect itself by taking up these factor H molecules and then inhibiting the activation of complement so the innate immune system won’t be so engaged.” This lack of activation allows the spores to remain in the host’s lungs, essentially hidden from the immune system.

The research was funded by a grant from the National Institutes of Health for over $1.4 million.

The team’s next step is to incorporate this knowledge into trying to make a better vaccine against the bacteria that cause anthrax.

“What this study tells us it that this interaction with the complement system has long-term consequences that were previously understudied, which has relevance to chronic infections,” Xu said. “This is really a very novel mechanism, and we think that it is not only applicable for anthrax, but also to other spore-forming pathogens, such as C. difficile. Now that we better understand how these organisms can evade the immune system, we have a better idea how to create a treatment to overcome their natural defenses.”

— Christina Sumners

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