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A Bad, Bad Bug

by Tara Anderson

Supported in her work by two prestigious fellowships from UK's Graduate School, Lisa Pedersen is studying a bacterium called Legionella. If you recall the TV ad where a kid at King's Island is water-rushed down the last turn of the giant slide and jetted out into the air, you have an image that may help you understand this bacterium.

Photo of Yousef Abu Kwaik and Lisa PedersenGraduate student Lisa Pedersen, with Yousef Abu Kwaik, is studying a bacterium called Legionella, which, if breathed in by humans, can cause flu-like symptoms, muscle aches, headaches, loss of appetite, and dry cough. Abu Kwaik is an associate professor in UK's Department of Microbiology.

Pedersen is studying one species of Legionella, called Legionella pneumophila. When the water that moves these bugs is contaminated and changes into aerosol form (water droplets small enough to be inhaled) the bacteria, if breathed in by humans, can cause flu-like symptoms, muscle aches, headaches, loss of appetite, and dry cough.

"I was interested in Legionella pneumophila and its system from the start," she says. "As soon as I met with Dr. Abu Kwaik and he told me about how L. pneumophila works to hijack the host cell, I was hooked. I found it fascinating, and jumped at the opportunity to work on it." Yousef Abu Kwaik is an associate professor in UK's Department of Microbiology.

"L. pneumophila causes two distinct illnesses," says Pedersen, who plans to graduate in May with a doctorate in microbial biology. "One of these, with symptoms lasting up to 48 hours, is usually taken care of pretty easily by the immune system." This brand of the disease is commonly referred to as Pontiac fever.

Potentially much more serious is the second illness, which can lead to pneumonia and, possibly, death. An outbreak of this cousin of Pontiac fever among persons attending a state convention of the American Legion in Philadelphia in 1976 led to the disease's name. In this outbreak, 180 people came down with pneumonia and 29 died.

Legionnaire's disease is transmitted through inhalation of contaminated aerosols generated by air-conditioning cooling towers (not window air-conditioner units), shower heads, drinking fountains, and jacuzzis. L. pneumophila is carried by amoeba that live in the water; no person-to-person transmission has ever been documented.

"When the bacteria-containing water droplets are inhaled, they enter the cells lining the air exchange regions of the lungs, the alveoli," Pedersen says. "If the immune system doesn't kill them, the bacteria can rapidly multiply and destroy the alveolar cells. Up to 50 percent of cases occurring in some hospital outbreaks have resulted in deaths."

Pedersen received a Kentucky Opportunity Fellowship for 1998-1999 and a Dissertation Year Fellowship for 1999-2000 through the UK Graduate School.

The key to preventing the onset of pneumonia is finding a way to target the bacteria's ability to multiply unchecked within macrophages, the body's seek-and-destroy militia, and other cells in the alveoli. Pedersen has already singled out some genes that allow the bug to thrive inside macrophages, and she is currently working on identifying other genes which are vital to the way L. pneumophila escapes its host cell and spreads to other cells in the lungs. "This work is important because if the bacteria can't break out of the host cell to infect other cells, they just eventually die inside the macrophages and the infection is stopped," Pedersen explains.

Anyone can be infected by L. pneumophila, but only about five percent of infections result in Legionnaire's pneumonia, with about 25,000 cases diagnosed in the United States each year. Those who catch this bug are most frequently the elderly, people with suppressed immune systems, and smokers. Legionnaire's pneumonia kills 15 to 50 percent of patients.

One reason to focus on L. pneumophila is that it is an excellent model for studying other bacteria, Pedersen says. "What we learn from L. pneumophila may be applicable to other intracellular bacteria, including those that cause more common diseases."

She says she has enjoyed her years in graduate school at UK. "I've learned how to solve problems, to design and develop experimental plans, and to draw sound conclusions from experimental data," she says. "I've also learned that not everything works the first time around."

Pedersen adds that not finding the expected answer is also an important research result. "That's not a bad thing, because sometimes a 'mistake' leads to new discoveries. It's a fantastic and exciting time to be in research," she says. "I have made good friends here, some of whom have graduated and now hold post-doc positions. Others have gone on to pursue other dreams, like med school."

"Lisa has been a very good graduate student," says Abu Kwaik. "She came to us not having done any research in her life, and has developed into a very good scientist within a short period of time. Over the past couple of years, she has developed her skills tremendously, and has become a great asset for our research program. It's always very rewarding to see a graduate student developing scientific skills. These are the future scientists who will make a difference."

Pedersen has been well supported in her work at UK. She received a Kentucky Opportunity Fellowship for 1998-1999 and a Dissertation Year Fellowship for 1999-2000 through the UK Graduate School. The $15,000 Kentucky Opportunity Fellowship is part of the Research Challenge initiative established in 1997; the Graduate School awarded 35 Kentucky Opportunity Fellowships in 1998-99 and another 35 for the current academic year. Dissertation Year Fellowships carry a stipend of $12,000 and cover full tuition.