Scientists Battle Bugs Using Genomics

Dec. 11, 2001 -- They are the James Bonds of the biological world.

Faced with a fierce lineup of human defenses, disease-causing bacteria and viruses use a range of tricks and gadgets to infect their hosts.

Some are willingly engulfed by the body's defense cells and then manipulate the cells to prevent their own destruction. Others carry needle-like structures to inject human cells with a protein "potion" that tricks the cells into allowing bacteria to enter. Some, like the plague-causing bacterium, can even program human defense cells to self-destruct.

The battles between disease-causing pathogens and the body's defenses have evolved into a complex arms race of sorts. To better understand those battles and find new ways of blocking infection, researchers have turned to genomics — the analysis of an organism's thousands of genes and the roles they play.

The work could prove vital in disabling the tools of bioterrorists — including anthrax.

Fighting Disease, and Bioterrorism

"We're trying to see which genes are turned on and when to learn how our host cells can respond better," said Philip Hanna, a biologist at the University of Michigan who studies how anthrax infects its hosts. "The last thing this world needs are weapons made from biology."

Under a new program called the Pathogen Functional Genomics Resource Center at The Institute for Genomic Research (TIGR) in Rockville, Md., scientists will have access to the more than 50 disease genomes that have already been decoded. These coded lists contain all the information a pathogen uses for launching its invasion on the body.

Now the goal is to learn which genes do what as a pathogen infects its host and how to stop them.

"You need to know what molecules in the bacteria attack the host in order to develop intervention mechanisms," said Carol Gross, a microbiologist at the University of California in San Francisco. "And bacteria are very clever."

Preventing Super Bugs

The six-year, $25 million contract might also help tackle what disease researchers say is a crisis in the making. Epidemiologists have long warned that overuse of antibiotics could prompt the development of medicine-resistant disease strains.

The recent outbreaks of anthrax, for example, spurred many to begin taking the antibiotic drug known as Cipro. Cipro fights the bacterium Bacillus anthracis by limiting the bacterium's ability to divide and multiply. But as more people take Cipro, scientists believe the bacterium gains more chances of evolving forms that can evade the drug's effects.

Rather than attacking viruses and bacteria directly — in ways that the pathogens can eventually resist — the new research center aims to find ways of helping the body resist infection.

Hanna and others have learned that anthrax invades its host by releasing a toxin that binds to a receptor on the outside of a host cell called a macrophage. Most bacteria are destroyed by macrophages, but anthrax bacteria somehow disable the cells and then flourish inside the cells' walls.

"What happens is the macrophages act as a doorway to your body," said Hanna. "It effectively chaperones the bug into your body."

Other pathogens, including those that cause tuberculosis, leprosy and Legionnaires' disease, also exploit the body's macrophage cells to infect their hosts.

New Targets for New Drugs

Although the anthrax bacterium has not yet been completely sequenced, Tim Read, a gene sequence specialist at TIGR, reports most of its genes have been detected.

"Once we know what the genes are then we can ask what genes are turned on during infection," Read said.

Meanwhile, Hanna is already putting the as-yet-unfinished genome information to use. By monitoring which genes are turned on during different phases of anthrax infection, Hanna is learning which genes are in charge as the bacterium penetrates a host's cells and creates a safe haven out of a normally hostile defense mechanism.

"Once we find responsible genes, then we can learn what genes new drugs should target," he said. "We hope this will lead to big breakthroughs."