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Using genes to spy on infections
Sunday, July 09, 2000 By Byron Spice, Science Editor, Post-Gazette
In the battle between humans and microbes, genes may be the ultimate spies. Someday, treatment for infectious disease may begin by doctors asking our genes for the identity of the bacterial or viral invader. Then, they may tackle the infection with drugs that target weak spots that they've identified by interrogating the microbe's own genes.
If necessary, doctors can then monitor the progress of the fight by checking on genes in both the victim's body and the invading microbe.
It's a war, said microbiologist Richard Young. No one said it had to be fair.
The trick will be to see which genes are turned on, or "expressed," in different cells. Young, of the Whitehead Institute in Cambridge, Mass., said this is already possible thanks to biochips and DNA microarrays -- technologies that can monitor changes in the expression of thousands of genes at a time.
The pattern of gene expression can change in response to any number of factors. If a person is under stress, for instance, various genes are switched on in different cells. Infectious agents also cause changes in gene expression as cells absorb injuries and mount their defenses.
Young said different microbes seem to generate different profiles of gene expression. Rather than identifying pathogens by isolating and culturing them, a process that can take days, it may be possible to rapidly identify them by genetically analyzing a few cells.
Most life on earth is microbial, Young noted, and most microbial life is poorly understood. That's why diagnostic tests are available for only a small subset of infectious agents.
But gene expression signatures might allow scientists to distinguish among many infectious agents without actually analyzing the germs themselves, just the way that, on a larger level, doctors can recognize the herpes virus that causes chickenpox by the kind of blisters it produces.
Gene expression also might be used as a way to identify particularly nasty bugs that merit further study.
Expression signatures also may prove to be an effective means of monitoring how the body is responding to treatment and for determining why some people are vulnerable to certain pathogens and why others aren't, said Young, 46, who is a graduate of Bethel Park High School.
Another approach that might yield better treatments for disease is enlisting the same techniques that were used to map the human genome to determine the genetic sequence of different bacteria.
Garth Ehrlich, director of the Center for Genomic Sciences at Allegheny General Hospital, said DNA sequencing of bacterial genomes might lead to new drugs, particularly against chronic infections, just the way that the sequencing of the human immuno-deficiency virus in the mid-'80s spurred development of the protease inhibitors that have since proven highly effective in treating AIDS.
The conventional view of bacteria is that they are single-celled microorganisms. But Ehrlich and other researchers have shown that bacteria actually like to live in colonies, called biofilms, in which they function much as a simple, multicellular organism.
"Biofilms may be [bacteria's] major mode of life in the wild," he added.
Bacteria in biofilms don't respond to antibiotics as readily as independent bacteria, he noted, because they don't divide as rapidly and don't express the same genes.
Analyzing the bacterial genome and understanding the genetic expression of biofilms will provide new targets for antibiotic development, Ehrlich predicted.
That will aid in treating infections that involve biofilms, such as chronic ear and sinus infections and the lung infections that often kill cystic fibrosis patients. Biofilms also plague implanted devices, such as cardiac pacemakers and urinary catheters.
Young said DNA microarrays will not be limited to the study of infections. "Much of the future of biology," he predicted, "will involve the use of arrays to understand what's happening to cells."
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