The Bubonic Plague's Pla Protein

Ben Weber, Kaitlyn Rothamer, Hailey Nuthals, Alex Esselman

(Dr. Colton and MSOE)

StudentsModelingAResearchTopic

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

The Bubonic Plague's Pla protein

2011-12 Topic

• "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

The Bubonic Plague

The Spread of the Black Death

• Characterized by swollen lymph nodes, fever, vomiting of blood, gangrene on fingers

• Death within 2-7 days.

Symptoms

• Only 10-30 cases of the plague are reported each year in the U.S.

• Globally, about 1,000-3,000 cases each year

In Today's Terms

Bubonic Plague in U.S.

• 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

Biological Warfare

Yersinia Pestis

• Y. Pestis is a gram negative bacteria• Gram negative: bacteria that are not affected by crystal violet

dye in Gram staining protocol.o Used to classify bacteria based on their cell walls

• Gram negative bacteria are known to cause swellingo Affects lipopolysaccharide layer (LPS)

Gram Negative Bacteria

Clotting is what the body uses to isolate bacteria

• Once clotted, white blood cells can take down bacteria

• Clots consist of fibrin

Where the Problem Starts: Clotting

• Pla prevents clotting (problem begins)

(Pla model pictures here)

• Cleaver: electrically excited water molecule

• Pla's cleaver cleaves active arm in antiplasmin & bond site in plasminogen

• Leads to more plasmin in blood.

Cleaving

• Antiplasmin attracts plasmin, pulls it out of shapeo Maintains healthy

levels of plasmin• Works to keep fibrin

intact• Intact fibrin = regular

clotting process.

Antiplasmin

Keep in mind - since Y. pestis is transferred through flea bites, blood tries to clot to kill it...

Example of cleaving

Antiplasmin pulling apart plasmin

Antiplasmin

• 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

Putting it Together

• 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)

How it Kills

Process of bubonic plague

• Y. pestis creates F1 & V antigens which prevent its absorption into cells

• Hides in white blood cells and lymph nodes to avoid detection from neutrophilso Neutrophils trap and kill microbes existing outside of

white blood cells

Sneaky Bacteria

< F1 antigen

V antigen >

No specific, tell-all immunization has been found... Possibilities:

• Vaccine made to target F1 and V antigenso This way the plague can't hideo Problem: many newer strains of Y. pestis are

drug resistant with altered antigens

Immunizations

• 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

When All Goes Wrong

• Though a problem in plagues, the cleaving reaction could be used for good instead of evil:o Cleaning oil spillso Better soaps o Cancer treatment/other medicines

Practical Uses

http://cbm.msoe.edu/stupro/smart/remote/step1.htmlhttp://en.wikipedia.org/wiki/File:Black_Death.jpghttp://www.themiddleages.net/plague.htmlhttp://alchemipedia.blogspot.com/2009/09/black-death-bubonic-plague-spread-in.htmlhttp://en.wikipedia.org/wiki/File:Acral_gangrene_due_to_plague.jpghttp://en.wikipedia.org/wiki/Black_Death#Symptomshttp://www.scifibloggers.com/top-10-diseases-worst-killers-in-history/http://members.tripod.com/miss_hand_history/warminster/alistair.htmhttps://encrypted-tbn2.google.com/images?q=tbn:ANd9GcRR649XpPnjB0BrMrOTt1oWc7hFgEeAxiFu9H62Td5cvcfy1cMJhttp://www.medicinenet.com/plague/article.htmhttp://image.shutterstock.com/display_pic_with_logo/154111/154111,1222961184,8/stock-photo-this-is-a-d-representation-of-the-yersinia-pestis-bacteria-better-known-as-the-bubonic-plague-18274534.jpghttp://www.visualphotos.com/photo/1x6040300/yersinia_pestis_bubonic_plague_bacteria_sem_b2201334.jpghttp://newsimg.bbc.co.uk/media/images/45390000/jpg/_45390167_002877261-1.jpghttp://www.bioinformaticonline.com/images/topics/pdb1.pnghttp://en.wikipedia.org/wiki/Gram-negative_bacteriahttp://en.wikipedia.org/wiki/File:Gram_negative_cell_wall.svghttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Clotting.htmlhttps://encrypted-tbn3.google.com/images?q=tbn:ANd9GcTGVOZ9dKPh9WII-miKkwK4RaO-BwUiBY3rW4xAFrRc_ebPE9k4Jghttps://encrypted-tbn0.google.com/images?q=tbn:ANd9GcQO8cB5XrZ9ti9D2M47R1TGQEORuKbV3_FNe6wwHwwmJsI-jHuPVwhttp://www.sigmaaldrich.com/img/assets/27040/fibrinogen-cleave.jpghttp://chemwiki.ucdavis.edu/@api/deki/files/10161/=image132.pnghttp://www.nostatic.com/proteins/Plasmin/plasmin.gifhttp://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001622/http://www.wisegeek.com/what-are-neutrophils.htmhttps://docs.google.com/presentation/d/1WH1stY5CsIrWUR77WzP5l8cTB0qpEifdRavuqbD2RE4/edit#slide=id.g114cf187_2_0http://upload.wikimedia.org/wikipedia/commons/thumb/0/00/Aspartyl_protease_mechanism.png/800px-Aspartyl_protease_mechanism.png http://www.dynamicscience.com.au/tester/solutions/war/biological/biologicalwrf.htmhttp://www.textmed.com/heatmaps/disease/bubonic-plague-us-heatmap.gifhttp://bioch.szote.u-szeged.hu/astrojan/protein/pictures/atpazf1a.gifhttp://mcl1.ncifcrf.gov/waugh_lcrv.htmlhttp://www.burdr.com/wp-content/uploads/2010/05/oil-spill-gulf-of-mexico-from-deepwater-horizon.jpghttp://beeyondthehive.com/store/media/thumbnails/HoneySoap

Bibliography

Protein Data Bank

Tools

Jmol(Tools ctd.)

Jmol• Java program used to view and

enhance understanding of molecular models

• Able to shape and control model

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

Acknowledgements