August 28, 2018

Joshua K. Hughey (North Carolina Central University)

Yersinia pseudotuberculosis to Yersinia pestis – Evolution of the deadliest pathogen in history

Yersinia pestis, as the causative agent for plague, is responsible for over 250 million deaths throughout human history. Of plague’s three manifestations, bubonic, pneumonic, and septicemic, the pneumonic iteration has the highest rate of mortality (~99%), and is the only one spread easily from human to human, via respiratory droplets. Due to its greater virulence and relative ease of transmission, pneumonic plague has remained a persistent threat, particularly in less developed nations. Pneumonic plague’s increased virulence may be attributed to its unique ability to remain undetected in the lungs of infected persons for approximately 36 hours post infection. Termed the pre-inflammatory phase, this time window gives the pathogen time to achieve a critical mass, giving it a foothold in overcoming host defenses. Recent research by lab and others indicates that this “immune inactivation” that characterizes the pre-inflammatory phase may be attributed, at least in part, to Y. pestis‘s ability to induce expressions of IL-1RA, a recepter antagonist for IL-1ß, a pro-inflammatory cytokine that plays a crucial role in mitigating acute bacterial infection.

Y. pestis evolved from a comparatively harmless soil bacterium, Yersinia pseudotuberculosis, approximately 15,000-22,000 years ago. In tracing the evolutionary lineage from Y. pseudotuberculosis to Y. pestis, the question my research asks is whether Y. pestis‘s ability to induce IL-1RA expression in immune cells is inherited from its evolutionary forebear, or if it is unique to the organism. The hope is that this understanding will provide insight into exactly when and how Y. pestis acquired this lethal adaptation.