The Bubonic Plagues Pla Protein Ben Weber Kaitlyn
The Bubonic Plague's Pla Protein Ben Weber, Kaitlyn Rothamer, Hailey Nuthals, Alex Esselman (Dr. Colton and MSOE)
SMART Team Students Modeling A Research Topic Purposes: To understand the molecular world through the application of science in analyzing facts Modeling proteins to understand the implications of their structural formulas • •
2011 -12 Topic The Bubonic Plague's Pla protein
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
The Spread of the Black Death
Symptoms • • Characterized by swollen lymph nodes, fever, vomiting of blood, gangrene on fingers Death within 2 -7 days.
In Today's Terms • • Only 10 -30 cases of the plague are reported each year in the U. S. Globally, about 1, 000 -3, 000 cases each year
Bubonic Plague in U. S.
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 • •
Yersinia Pestis
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. o Used to classify bacteria based on their cell walls Gram negative bacteria are known to cause swelling o Affects lipopolysaccharide layer (LPS)
Where the Problem Starts: 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) • • •
(Pla model pictures here)
Cleaving • • • Cleaver: electrically excited water molecule Pla's cleaver cleaves active arm in antiplasmin & bond site in plasminogen Leads to more plasmin in blood. Antiplasmin • • • Antiplasmin attracts plasmin, pulls it out of shape o 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. . .
Example of cleaving
Antiplasmin pulling apart plasmin
Antiplasmin
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
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)
Process of bubonic plague
Sneaky Bacteria • • Y. pestis creates F 1 & V antigens which prevent its absorption into cells Hides in white blood cells and lymph nodes to avoid detection from neutrophils o Neutrophils trap and kill microbes existing outside of white blood cells < F 1 antigen V antigen >
Immunizations No specific, tell-all immunization has been found. . . Possibilities: Vaccine made to target F 1 and V antigens o This way the plague can't hide o Problem: many newer strains of Y. pestis are drug resistant with altered antigens •
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
Practical Uses • Though a problem in plagues, the cleaving reaction could be used for good instead of evil: o Cleaning oil spills o Better soaps o Cancer treatment/other medicines
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Tools Protein Data Bank
Jmol (Tools ctd. ) Jmol Java program used to view and enhance understanding of molecular models Able to shape and control model • •
Acknowledgements • • • Dr. Colton (MSOE SMART team program) MSOE Center for Biomolecular Modeling Mr. Heeren (Local SMART team leader)
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