“Mycobacterium tuberculosis is the world’s most successful pathogen.”
said Denise Kirschner, a professor of microbiology and immunology at U-M. “It’s the #1 cause of death due to infectious disease in the world.”
It has also been around for a long time, claiming victims as varied as Eleanor Roosevelt, Frederic Chopin, John Keats and the ancient Egyptian Irtyersenu. While it is best known for conspicuous symptoms such as coughing up blood, the secret to its success is in its insidious, latent form. Only about 10 percent of people infected with the bacteria get active TB right away – the other 90 percent might not even know they harbor the bug.
A person with a latent TB infection has no symptoms and cannot transmit the disease. Instead, the bacteria wait for a moment of weakness that may come in the form of age or illness, such as HIV. Then they may have the opportunity to infect a new population. “We don’t understand why some people develop active or latent disease or why the latent disease reactivates,” said Kirschner.
Tough to Treat
In spite of our incomplete understanding of TB, we can successfully treat it with antibiotics. The trouble is that the regimen, which requires multiple drugs, can last as long as nine months to a year. The slow pace is necessary to prevent excessive inflammation in the lungs. Inflammation leads to scar tissue, which makes it difficult to breathe if the lungs can’t expand properly.
In latent tuberculosis, the immune system achieves a stalemate, with enough healthy white blood cells to maintain the perimeter while the bacteria survive inside the infected macrophages.
Unfortunately, humans don’t always put up with long treatments well, especially when we no longer feel sick. Once TB retreats to its latent stage, the harsh side effects and cost of treatment – especially when TB is most common in some of the poorest regions of the world – are strong incentives to stop taking the drugs. This spurs the evolution of resistant strains.
The search for new and better treatments hinges on answering two questions: How can we maintain the latent phase, keeping TB from progressing to its contagious and deadly full-blown form? And how can we encourage the immune system just enough that it kills off the TB bacteria more quickly without creating scar tissue? Over a decade ago, Kirschner joined forces with JoAnne Flynn, a professor of microbiology and molecular genetics at the University of Pittsburgh, PA, to begin answering these questions. In 2005, they welcomed Jennifer Linderman, professor of chemical engineering at U-M, to their team.