Researchers find key to tuberculosis persistence i...( The tuberculosis bacterium requires a...)

The tuberculosis bacterium requires a specific enzyme to cause persistent infection, a consortium of researchers at Rockefeller University and three other institutions have found. The discovery suggests that targeting the enzyme could improve therapies for TB, which claims more lives each year than any other infectious disease.

The finding, published in the Aug. 17 issue of the journal Nature, resulted from a multidisciplinary effort by investigators at Rockefeller, Albert Einstein College of Medicine, Washington University in St. Louis and Texas A & M University, each of whom focused on different aspects of the problem.

The enzyme produced by the bacterium, isocitrate lyase (ICL), allows the TB microbe Mycobacterium tuberculosis to use fatty acids as a source of energy. Fatty acids are the most abundant source of stored energy in the body's cells. The new findings suggest that these reserves may be exploited by "intracellular" pathogens like M. tuberculosis, which make their living by parasitizing the cells of the host. The researchers have shown in a mouse model of TB that disabling the gene for ICL in M. tuberculosis crippled the bacterium in the disease's later, persistent phase.

"If we can block an enzyme that allows M. tuberculosis to persist, that might provide an avenue for attacking the bug in its latent phase," says lead author John McKinney, Ph.D., assistant professor and head of Rockefeller's Laboratory of Infection Biology. "A drug that targeted persistence would be quite different from conventional drugs, which target processes required for bacterial growth. ICL is not present in humans and other vertebrates, so blocking its activity should not cause harmful side effects in the host."

When M. tuberculosis infects the body, the immune system rallies to fight the invader but is unable to eradicate the microbe completely. A stalemate is achieved in which the bacteria continue to live in infected tissue, although they are not multiplyi
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Contact: Jim Stallard
stallaj@rockvax.rockefeller.edu
212-327-8977
Rockefeller University
16-Aug-2000