Meningitis: The Smooth Criminal

Trevor Kraeger, Tyler Stokka, Jordan Williams, Chris Werner, Kassidy Branning, Anna Grim, Ben Weber, Emily Mytinger, Kaitlyn Rothamer, and GBH!

SMART Team Project 2011

Common Cold or Something Worse???

Fever

Persistent headaches

Vomiting

Stiff and painful neck

Seizures

Skin rash

Dizzy spells

Statistics of Meningitis

1,500 infected annually

900-3,000 reported cases annually

Occurs in adolescents and young adults

1 out of every 7 adolescents will die

Are you caught up on your vaccinations???

What Exactly is Meningitis???

Swelling of the meninges

Bacterial and viral

Viral more common

Bacterial is deadly

Outbreaks prevalent in close quarters

Permanent effects

Meningitis Across the Globe

A Little Closer To Home

Neisseria meningitidis

Gram Negative bacteria

Has an extra cell membrane

Thinner peptidoglycan layer

More complex (two zones rather than one)

Gram Negative: Why it is important

Evade and Invade

How does this happen???

Penetration of the blood brain barrier (BBB)…

…through the help of heparin, fibronectin and OpcA

Secret Agent Analogy

via pilius interactions, OpcA

opca interactions with the heparin and fibronectin or vitronectin

another Heparin sulfate proteoglycan receptor method

Three different ways to

Get Into the Cell

The 3 Major Proteins Key to Infiltration

“Arm” of bacterial Meningitis

Has a polar positive region in the notch on the “front”

Mainly consists of a Beta Barrel

A component of Blood serum

a highly-sulfated long unbranched polysaccharide

an anticoagulant

Highest negative charge density of any known biological molecule!

2 Heparin Binding Sites

Integrin Binding site!

Meningitis Passing through Unnoticed

OpcA positive groove binds to negative Heparin

Heparin bind to positive fibronectin sites (two sites)

Fibronectin attaches to the integrin on the exterior of the blood-brain barrier

Receptor Mediated Endocytosis

How to Prevent Meningitis from penetrating the BBB

Methods of prevention

OpcA positive groove

Nothing is successful yet

With the technology of today currently expanding it will only be a matter of time before a mechanism is found.

S.M.A.R.T. Team

Students

Modeling

A

Research

Topic

Our Mission…To perform background research on how meningitis works.

To model the proteins involved using JMOL

To give a kick butt presentation on meningitis and how it infiltrates the BBB!

After the above 3 objectives are completed, report back to GBH for your next assignment.

Not as Easy as You Think

Starting from Scratch

X-ray Crystallography

XYZ Data: Caterpillar to Butterfly

Protein Data Bank

Scientists make the protein data available to the public.

Acknowledgments Dr. Shannon Colton

MSOE/ Center for Biomolecular Modeling

SMART Team Program Other Smart team groups at DCE

Oh…btw…

…WE FOUND WALDO!!!

You probably didn’t notice him up there during the entire presentation, did ya???