Exploring Black Death through 3D Modeling of the Plasminogen Activator Protein

Abstract

Black Death, caused by Yersinia pestis, originally had a 40–75% mortality rate, with a risk of the disease maturing into the pneumonic and septicaemic phases. With current threats of using Y. pestis as an agent of biological warfare, studying how the virulency of the disease is important as the bubonic plague could be a potent weapon. A recently discovered potential treatment would inhibit the omptin (outer‐membrane protease) Pla, which cleaves the R561–V562 bond in the amino acid sequence of plasminogen, converting it to plasmin: an enzyme that degrades proteins in blood plasma such as fibrin. This leads to a lack of clotting, thus enabling the bacteria to gain entry into the host organism. Y. pestis injects toxins in immune cells, killing these cells. The result is a depressed immune response. However, if Pla is inhibited, then the mortality rate decreases as there is no progression to the pneumonic phase (quantized by the lack of change of fluid in the lungs). A lack of Pla would mean that the plague would not spread into other areas of the body, localizing the disease and making it possible to treat. Because the bubonic plague is a disease that kills in 2–7 days, inhibiting Pla would increase the window for treatment. The Torrey Pines SMART Team (Students Modeling A Research Topic) modeled the Pla protein using 3D printing technology. Supported by a grant from the HHMI Pre‐ College Program.