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New Findings on Drug Tolerance in TB Suggest Ideas for Shorter Cures

New findings on how tuberculosis (TB) bacteria develop multi-drug tolerance point to ways TB infections might be cured more quickly. The results identify both a mechanism and a potential therapy for drug tolerance that is induced in the TB bacteria by the host cells they infect.

The study will be published April 1 in the journal Cell.

Currently, TB treatment requires a complex, long-term curative regimen of at least six months, explained the senior author of the study, Dr. Lalita Ramakrishnan, University of Washington (UW) professor of medicine, microbiology and immunology. Her lab conducted the study in collaboration with Dr. Paul Edelstein, of the Department of Pathology and Laboratory Medicine at the University of Pennsylvania.

Many months of TB treatment are needed because the bacteria become tolerant to TB drugs. In the first couple days of treatment the bacteria die rapidly, but the death rate then slows to a crawl as the bacteria become resistant to killing. This tolerance to antibiotics occurs despite the absence of genetic mutations for drug resistance.

The authors noted that adhering to six months of drug treatment is difficult, particularly in areas of the world where TB is prevalent.

"Breaks in treatment can lead to relapses that perpetuate the TB epidemic and also fuel the development of genetic resistance to treatment," Edelstein said.

An urgent goal of scientists is to overcome drug tolerance, yet most of the drugs in development will not shorten the lengthy treatment. This failure results from a poor understanding of the mechanism of TB tolerance.

"Drug tolerance," Ramakrishnan said, "has been largely attributed to TB bacteria that are dormant in the body and not reproducing. These postulated dormant bacteria are thought to be unaffected by the administered antibiotics that are most effective against rapidly growing organisms"
 
 

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