Implementing a Crosslink Within Protective Antigen of Bacillus Anthracis

Overview

Anthrax is a vicious disease caused by the bacterium Bacillus anthracis. While anthrax is a very rare disease within the United States, it is fairly common in agricultural regions. One of the reasons anthrax is dangerous is because it can stay dormant for very long periods of time in the form of spores. One of the key goals of my research is to inhibit the ability of the anthrax bacterium to cause widespread disease. The goal of the project at a theoretical level is to ultimately test the stability of PA of Bacillus anthracis when a crosslink is placed that links two residues of PA together. B. anthracis secretes an exotoxin which has 3 components: the protein, protective antigen (PA), and two enzymes, edema factor (EF) and lethal factor (LF). PA creates a funnel that binds to one of two receptors, TEM8 or CMG2, penetrates the host cell's cell membrane, and allows edema factor and lethal factor to easily attack the cell. Upon PA’s unfolding, T298 and N601 are completely separate from each other. However, under normal circumstances T298 and N601 of PA are very close to each other. The hypothesis is that a cross-link (a disulfide bond) can be created under normal circumstances (before unfolding) that will prevent the unfolding process of protective antigen. Understanding how the crosslink affects the pore formation of B. anthracis could provide insights into how pore formation occurs, and keep the protein from undergoing a conformational change to penetrate the cell membrane which would then prevent the entry of the enzymes EF and LF. Humans could be inoculated with live strains of anthrax, rendered powerless by the crosslink, to create a better immune response in the body than current vaccines which use dead strains. I conducted this experiment because it was within the grasp of my understanding and because it was previously unexplored. Crosslinking has been around for a long time, but attempts to figure out how PA unfolds are new and the specific mutant that I created could yield important results. A crosslink could prevent this behavior and allow for a better understanding of how PA unfolds as well as have several interesting applications.

Competition history

• AJAS 2019 Category not listed

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