Pla : The Reaper’s Scythe

1. Pla: The Reaper’s Scythe Presented by: Tyler Stokka Advisor: Mr. Heeren Overseer: Dr. Colton cbm MSOE http://images2.fanpop.com/image/photos/12000000/Grim-Reaper-the-grim-reaper-12078702-787-873.jpg

2. The Black Plague: Taker of Life • 1348-1350 AD • 20 Million lives claimed at the time… • Almost 1/3 of Europe’s Population • Transferred by: Rats and Fleas • That was Just a pandemic of the past, so we’re safe now right??

3. The Black Plague and You • About 10-15 cases per year in the U.S. • 1,000 to 3,000 cases globally per year • Today’s Medicine: 1 in 7 cases (versus 40-60% in the past) are fatal • It is a likely option for bioterrorism because of how easy it can spread http://2.bp.blogspot.com/_CAoFDpupTaY/SXSc7TPmGnI/AAAAAAAABfo/gw6x3pJCqVc/s400/PLAGUE+FLEA.jpg

4. Notice the Correlation between the two  http://staff.bbhcsd.org/vendelc/world98.gif

5. Why So Deadly? The Method The Means The body’s usual response to pathogens (clotting) The Pla protein in Yersinia Pestis is utilized for evasion It essentially is like trying to handcuff a criminal who has access to bolt cutters. • Transfers through the rapid diffusion of rats harboring infected fleas These factors allow Yersinia Pestis to wreak havoc and get away with it! http://t0.gstatic.com/images?q=tbn:ANd9GcSsOgi36Ls8V7M4AnpXu3fiI4KAiajVYbD_Sc0hJsOVx-vjdq10BiP-jbY0mw

6. Yersinapestis • Gram-negative Bacteria • In the Enterobacteriaceae family • 1 of 11 species, 3 of which are threatening to man • Spread by numerous rodents and fleas • Slows and Stops the clotting process in Humans • Similar to more commonly known E. coli http://upload.wikimedia.org/wikipedia/commons/1/15/Yersinia_pestis_fluorescent.jpeg http://jencarey.files.wordpress.com/2011/08/800px-smallpox01.jpg http://vs8.tripod.com/bubon.jpg

7. Yersinapestis • It being Gram-negative gives it an extra defense • Has two cell walls accompanied by periplasmic space • Extra cell wall acts as armor, preventing damage • This gives it resistance to penicillin and lysozome • Taking danger to a whole knew level http://homepage.ntlworld.com/diamonddove/04a_Gram/Gram.h25.jpg

8. Special Protein in the Outer Wall • The omptinPla • (Omptin- a type of bacterial protease that cleaves peptides with the help of a water molecule) • Pla is the Key to Yersinapestis’ devastative success • Has the roles of activating plasmin and cleaving anti-plasmin • This promotes fibrinolysis yielding a clot-less fate LPS Binding Motif http://www.simplylefty.com/images/image/Products/Articles/Scissors-figure1.jpg http://img.tfd.com/wn/B4/64AB8-limb.png

9. Once behind enemy lines… • Body has many defense mechanisms against pathogens (Physical Barriers, T-Cells, B-Cells, lymph system, inflammation, etc…) • One of the most prominent is Coagulation, or “trapping” the pathogen inside of a clot • Some pathogens (such as Y. Pestis) have built up a resistance to body defense • In this case, Pla is able to maneuver around the coagulation response

10. What goes down Y. Pestis is then granted “unlimited access” to wreak havoc throughout the host! Body of the Host Transfer to host through fleas and various vermin Y. pestis’ serpinPla then activates plasminogen (inactive form of plasmin) which then starts cleaving fibrin. . . Clearing the clot “net”… Body attempts to capture the pathogen YersinaPestiswith coagulation, or in other words, capture it using a “fibrin net” clot.

11. Pla’sDirty Deeds • Pla does two major things that promote fibrolysis: • Activates plasminogen to it’s active form plasmin  cleaves fibrin • Cleaves anti-plasmin which allows plasmin to continue lysing

12. Alpha 2 Anti-Plasmin • Inhibits Plasmin • Cleaved by Pla • Important for normal coagulation (clotting)

13. Therefore. . . • Too much plasmin = bleeding disorder • Too much antiplasmin (inhibitor) = clotting disorder www.microbiologyonline.org.uk/themed/sgm/img/slideshows/3.3.2_immune_2.png

14. Signs of the plague http://www.scifibloggers.com/top-10-diseases-worst-killers-in-history/ http://www.google.com/imgres?num=10&um=1&hl=en&safe=active&rlz=1C1TSNO_enUS463US463&biw=1241&bih=606&tbm=isch&tbnid=6Auai3wuxUDK7M:&imgrefurl=https://sites.google.com/a/apps.edina.k12.mn.us/2011s2-12b-bubonic-plague/home/symptoms&docid=P9w5kYrrRcrIbM&imgurl=http://www.glogster.com/media/5/16/52/28/16522831.jpg&w=367&h=489&ei=30ewT46GBqKC2AWt1OTpCA&zoom=1&iact=hc&vpx=617&vpy=224&dur=185&hovh=259&hovw=194&tx=83&ty=184&sig=113969962684917488505&sqi=2&page=1&tbnh=119&tbnw=93&start=0&ndsp=22&ved=1t:429,r:11,s:0,i:96 http://sidesinger.wikispaces.com/file/view/plague.jpg/43064813/plague.jpg

15. Clueless… • Scientists to this day still do not understand how the Bubonic plague killed people so fast • Some believe it can be accredited to: • immunizations weren’t invented yet • climate affected immunity • sanitation was bad.

16. How do they know?? • X-Ray Crystallography!

18. Protein Data Bank

19. J-mol: Miracle Worker

20. Extreme Makeover: Protein Edition

21. On the Shoulders of Giants • These Processes make our research and investigation possible. . . • Wait a sec, who’s we? • . . . • We are SMART Team!! • Students Modeling AResearch Topic • An awesome program provided by MSOE

22. 3 Steps to being SMART • Background Research • J-mol software • Biochemistry • The topic • Develop the Story, Model the Proteins • Presentation

23. Rough Reading

24. You don’t have to be TOO smart, to DO SMART!

25. Brief Bibliography • http://www.militaryhistoryonline.com/general/articles/BlackDeath.aspx • http://plague.emedtv.com/yersinia-pestis/yersinia-pestis.html • http://en.wikipedia.org/wiki/Gram-negative_bacteria • http://www.maexamhelp.com/id106.htm • http://www.pbs.org/newshour/bb/health/july-dec11/blackdeath_10-13.html • http://en.wikipedia.org/wiki/Omptin

26. Acknowledgments • Dr. Shannon Colton • MSOE/ Center for Biomolecular modeling • SMART Team Program • Overseer: Mr. Heeren • This year’s SMART Team Crew: