Published in CenterView October 26, 2009
Microbiology chairman's research battles Staphylococcus of the eye
When a person's eye gets a bacterial infection, Dr. Richard O'Callaghan knows the stakes: It's a battle between a trio of destructive forces and a trinity of goodness.
Photo by Jay Ferchaud
Dr. Richard O'Callaghan, center, professor and chair of
microbiology, works with Anastasia Weeks, lab tech. Dr.
Armando Caballero, right, prepares research material.
Vision hangs in the balance. That's why O'Callaghan, chairman of the Department of Microbiology at the University of Mississippi Medical Center, applied for — and this summer received — a federal grant continuation of nearly $1.5 million.
The funding will continue his 15-year study of bacterial infections of the eye.
"When an eye gets infected with bacteria, either nothing happens or everything happens," he said. "Some bacteria can be introduced, reproduce by the millions, but there is no tissue dammage and the eye can still function well. Other bacteria will irreparably damage the eye."
The nastiest bacteria, and some of the most common to attack the cornea, are Staphylococcus, the subject of the grant he received from the National Institutes of Health through its National Eye Institute.
When Staph infects the cornea, that destructive trio comes into play. First, the bacteria replicate, second, release toxins and third — somewhat counterintuitively — the body's own immune system further damages vision as it tries to fend off the infection.
Antibiotics, first in the trinity of goodness, can wipe out most bacterial infections. Secondly, steroids will suppress the person's immune system. That leaves the toxins, the most damaging of which is called alpha toxin, floating around, wreaking havoc.
"We've been wishing and hoping for a way to stop this toxin," O'Callaghan said.
Actually, he's been doing a lot more. O'Callaghan began the study at Louisiana State University where, in about 1994, the NIH began funding his ocular research.
Selling his house and moving to Jackson from Slidell, La. — just months before Hurricane Katrina — O'Callaghan returned to UMMC, his alma mater, where he had earned his doctorate in 1970.
His research in Louisiana had led to the discovery of a third member of the trinity: an inhibitor to counteract the toxins. It's a cream-filled doughnut of sorts.
"It's actually a form of cholesterol. When introduced into the eye, in some way or another, it stops the toxin," he said. "You have to make the cholesterol water-soluble and the only way to do that is to put a cholesterol molecule into the middle of a cyclodextrin molecule."
Cyclodextrin, at the molecular level, is just a ring of seven glucose molecules. Put the cholesterol into it like filling into a doughnut and drop it into the eye.
Simple, right? After all, what are cream-filled doughnuts if not sugary vehicles for conveying scoops of cholesterol?
"The NIH wants me to see if there are other inhibitors that work better than cholesterol," he said. "And they want me to see if it will work in conjunction with an antibiotic and a steroid. That could be a very helpful cocktail."
Dr. Bo Huang in the Department of Ophthalmology plans to collaborate by testing inhibitor candidates, O'Callaghan said. Dr. Mary Marquart, associate professor of microbiology, is studying the imune response.
A second part of the grant continues research on the toxins themselves. Collaborating with Dr. Timothy Foster at Trinity College in Ireland, the researchers knocked out genes that make alpha toxin from their strain of Staph.
They found another toxin, called gamma toxin. Knocking out the genes for that, they found a third toxin, protease, O'Callaghan said.
Removing the genes for protease was a big challenge, O'Callaghan said, but Dr. Armando Caballero, assistant professor of microbiology, did it.
To figure out just how potent the protease toxin is, scientists in O'Callaghan's lab are now comparing the toxin-less bacterial strain with the protease-making strain.
As the battle of bacterial infection continues, it may be O'Callaghan and his collaborators who keep the vision winning.