TUESDAY, Dec. 9, 2003 (HealthDayNews) -- Mycobacterium tuberculosis is perhaps the most effective human pathogen, infecting a third of the world's population.
From the perspective of evolution, TB is an exquisitely well-designed bug, able to lie dormant in its hosts for decades without arousing a lethal immune response or deadly symptoms that might kill off its prey.
Now, a team of scientists has stumbled upon a possible explanation for TB's venerable symbiosis. They got there by accident. Trying to alter the genetic makeup of TB's surface proteins to weaken it, the researchers turned the bug into an potent super germ.
"We initially disrupted the set of genes [called mce1] that were believed to play a role in bacterial entry into the host cell," says Lisa Morici, a microbiologist at Tulane University and a member of the research group. "We thought that might lead to a vaccine candidate" or a novel approach to antibiotic treatment.
"We were quite shocked when the result was hyper-virulent," says Morici, who conducted the work while a graduate student at the University of California at Berkeley.
Normally, people infected with tuberculosis are able to keep the infection in a holding pattern, or latent state in which it neither disappears nor advances. But mice infected with the supe germ couldn't mount a robust immune response to the bacteria, leaving them vulnerable to sweeping disease and death.
The genetic change appears to prevent mice from forming structures called granulomas, marshmallow suits of immune cells that surround TB bacteria and prevent them from infecting other tissue.
In other words, Morici says, the mouse immune system doesn't seem to recognize the mutant germ, leaving itself open to an overwhelming infection.
Yet the change in the long run would be lose-lose, she adds. Granulomas protect not only hosts but TB itself. Without them, the bacteria likely would be too deadly to spread widely. "We've always thought that that granuloma formation was host-protective; it walls [TB] off from causing further damage. But the bacteria are still alive in there. TB has evolved to take advantage of that, and later on in life it will reactivate and spread."
The gradual flagging of the immune system with age or a different infection may spring TB from its sleeping state.
The researchers report their findings in this week's issue of the Proceedings of the National Academy of Sciences.
Dr. Eric Rubin, a TB researcher at the Harvard School of Public Health, calls the latest work "really cool. It's going to tell us a lot about what TB does."
However, Rubin cautions, mouse models of TB differ significantly from the way the pathogen behaves in the environment: It doesn't naturally infect rodents, for starters, preferring humans as its targets. In addition, TB's genome is highly labile, losing DNA frequently. As a result, he says, scientists should by now have seen the hyper-virulent mutation in human TB. "One would think you'd see outbreaks" of the strain in nature, he says.