1. The Bubonic Plague's Pla Protein
Ben Weber, Kaitlyn Rothamer, Hailey Nuthals, Alex Esselman
(Dr. Colton and MSOE)

2. Students Modeling A Research Topic SMART Team Purposes:
To understand the molecular world through the application of science in analyzing facts
Modeling proteins to understand the implications of their structural formulas

3. The Bubonic Plague's Pla protein
Topic
The Bubonic Plague's Pla protein

4. The Bubonic Plague "The Black Death"
First occurred in the Byzantine Empire (500 AD), where it killed about 25 million people
Next hit Europe in the 1330's, killing nearly 1/3 of the population.
Spread from flea bites that jumped rides on trade ships from China to Italian ports
Caused by bacteria Yersinia Pestis

5. The Spread of the Black Death

6. Symptoms
Characterized by swollen lymph nodes, fever, vomiting of blood, gangrene on fingers
Death within 2-7 days.

7. In Today's Terms
Only cases of the plague are reported each year in the U.S.
Globally, about 1,000-3,000 cases each year

8. Bubonic Plague in U.S.

9. Biological Warfare
Earliest use of biological warfare - Chinese warriors would launch dead bodies infected with plague using catapults
Infected and killed enemies
rapidly
Today...
Could be used as a terrorism weapon - quickly causes epidemic
If made to be drug resistant, could be even more horrible

10. Yersinia Pestis

11. Gram Negative Bacteria
Y. Pestis is a gram negative bacteria
Gram negative: bacteria that are not affected by crystal violet dye in Gram staining protocol.
Used to classify bacteria based on their cell walls
Gram negative bacteria are known to cause swelling
Affects lipopolysaccharide layer (LPS)

12. Where the Problem Starts: Clotting
Clotting is what the body uses to isolate bacteria
Once clotted, white blood cells can take down bacteria
Clots consist of fibrin
Pla prevents clotting (problem begins)

15. (Pla model pictures here)

16. Cleaving
Antiplasmin
Cleaver: electrically excited water molecule
Pla's cleaver cleaves active arm in antiplasmin & bond site in plasminogen
Leads to more plasmin in blood.
Antiplasmin attracts plasmin, pulls it out of shape
Maintains healthy levels of plasmin
Works to keep fibrin intact
Intact fibrin = regular clotting process.
Keep in mind - since Y. pestis is transferred through flea bites, blood tries to clot to kill it...

17. Example of cleaving

18. Antiplasmin pulling apart plasmin

19. Antiplasmin

20. Putting it Together Pla's cleaver increases plasmin
More plasmin means less fibrin
Less fibrin means less ability to clot
If there are no clots, Y. pestis is free to travel the human body

21. How it Kills
Y. pestis begins to attack the lymphatic system (bubonic plague)
Can spread to respiratory system (called pneumonic plague)
Can also affect blood system (called septicemic plague)

22. Process of bubonic plague

23. Sneaky Bacteria
Y. pestis creates F1 & V antigens which prevent its absorption into cells
Hides in white blood cells and lymph nodes to avoid detection from neutrophils
Neutrophils trap and kill microbes existing outside of white blood cells
< F1 antigen
V antigen >

24. Immunizations
No specific, tell-all immunization has been found... Possibilities:
Vaccine made to target F1 and V antigens
This way the plague can't hide
Problem: many newer strains of Y. pestis are drug resistant with altered antigens

25. When All Goes Wrong
Without immediate treatment, the plague can spread and kill quickly
Plague has possible mutations to resist antibiotics
Unless we understand how this plague works, a second, more fatal form could spread

26. Practical Uses
Though a problem in plagues, the cleaving reaction could be used for good instead of evil:
Cleaning oil spills
Better soaps
Cancer treatment/other medicines

27. Bibliography http://cbm.msoe.edu/stupro/smart/remote/step1.html

28. Tools
Protein Data Bank

29. (Tools ctd.)
Jmol
Jmol
Java program used to view and enhance understanding of molecular models
Able to shape and control model

30. Acknowledgements Dr. Colton (MSOE SMART team program)
MSOE Center for Biomolecular Modeling
Mr. Heeren (Local SMART team leader)