Bacterial Barbarians

This story appears in the spring 2015 issue of 360:The Magazine of San Diego State University.

On the list of body parts you don’t want to become infected, the brain is right there at the top. Luckily, the blood-brain barrier manages to keep out most of the unwanted guests. The barrier primarily consists of a thin strip of endothelial cells in the central nervous system that form so-called tight junctions between themselves.

Like a bouncer at a ritzy nightclub, the barrier is highly selective about who it lets inside. Unfortunately, bacteria can sometimes fool these cells into letting down their guard, causing deadly bacterial meningitis. San Diego State University biologist Kelly Doran studies the how these sly bacteria slip by the brain’s defenses—advancing both the state of science and the careers of her students.

Breaking barriers

For Doran, the fight is a personal one. Her younger sister died as teenager as a result of complications arising from the bacterial meningitis she’d had since birth.

“I don’t think I consciously set out to solve this problem, but at each step in my education and then my career, I found myself following this path,” Doran said.

In her lab, Doran and her students and postdoctoral scholars explore the cellular mechanisms that the bacteria exploit in order to gain entry to the brain. The cells that make up the blood-brain barrier can selectively allow through immune cells by temporarily dissolving the tight junctures between themselves, and these bacteria have found a way to activate the cellular signals that break down the junctures.

“The bacteria are highjacking the normal systems of the cell,” Doran explained. “It makes the barrier leaky which contributes to disease.”

Preparing the future

But exactly how the bacteria do this remains a mystery. Doran is experimenting with a number of different models to figure out what’s going on. One of her latest attempts involves a collaboration with the University of California, San Diego, in which she and her colleagues can watch in real-time as group B streptococcus bacteria infiltrate the blood-brain barrier of see-through zebrafish larvae.

By experimenting with specially grown strains of zebrafish, the researchers are able to “turn off” various genes to see what effect that has on the bacteria’s ability to cross the barrier.

Although she’s a highly respected researcher in her field and enjoys the work, Doran’s true passion is in preparing the next generation of scientists and doctors. She measures her success by how well she is able to involve students in her research and whether they achieve their own research victories.

“That is primarily what I love,” Doran said. “I see my main impact as giving students the tools and support they need to accomplish their goals.”