Yersinia pestis is such a virulent pathogen due to its multiple virulence factors. Although the pathogenesis of plague is not clearly understood, it is known that Y. pestis utilizes such virulence factors as the Yops plasmid, Type III Secretion System, as well as producing a number of antigenically distinct molecules, including toxins, which contribute to disease progression.
The V and W antigens of Yersinia pestis cell walls are protein-lipoprotein complexes that inhibit phagocytosis. Another antiphagocytic antigen is called the F1 antigen whose genes are located on a plasmid. This serves an interesting purpose because it has the ability to obtain iron from the host. The F1 antigen also is partly responsible for Y. pestis survival in the gut of the flea. It blocks flea digestion making the flea seem “starved” even after a blood meal. Therefore, the flea jumps around from host to host in a futile effort to feel full which is another unique aspect of how plague spreads so quickly in such a short period of time. An exotoxin that is toxic to mice, however might not be involved in pathogenesis of human plague, is called murine toxin. It is a respiratory inhibitor that blocks mitochondrial electron transport reactions at the point of coenzyme Q. It can produce systemic shock, liver damage, and respiratory distress in mice, although all of these symptoms also occur in human plague. Y. pestis also has a factor called the plasminogen activator which helps disseminate the bacteria through the body quickly, helping the disease progress at a faster rate.
Probably the most important factor aiding in its pathogenesis is the Ysc-Yop Type II Secretion System. Once inside the host, Y. pestis build the Ysc injectisome which involves all of the Yscs coming together to form a structure comprised of 27 proteins which function as a syringe-like organelle spanning the cell membrane and anchored in the inner and outer membranes. This Type III Secretion Syste achieves contact with the host cell via adhesions and integrins on Y. pestis. Yop B and Yop D are transported through the injectisome by ATP hydrolysis into the host cell membrane. Once inserted into the cell membrane, effector Yops disrupt the actin cytoskeleton of the host cell membrane. This system gives Y. pestis the ability to evade phagocytosis, preventing an inflammatory response which leads to massive tissue colonization.
Recently, a new virulence factor was discovered by researchers and its function is to prohibit destruction of Y. pestis in the flea gut allowing for colonization. Although the exact molecular mechanism for protection is not yet understood, it has been found that Y. pestis picked up a gene encoding an enzyme called PLD from an unrelated bacteria. Upon infecting fleas with Y. pestis variants which either contained or lacked the PLD gene, it was shown that PLD is necessary for Y. pestis flea gut survival.
Madigan, Michael T., John M. Martinko, and Jack Parker. Brock Biology of
Microorganisms. Prentice Hall Publications, NJ. 2003