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Gene mutation leads to super-virulent strain of TB

Berkeley - Disabling a set of genes in a strain of the tuberculosis bacteria surprisingly led to a mutant form of the pathogen that multiplied more quickly and was more lethal than its natural counterpart, according to a new study led by researchers at the University of California, Berkeley.

As early as two weeks after infection, researchers found significantly more bacteria from the organs of mice infected with the mutated tuberculosis (TB) bacteria than for mice infected with the unmodified, or "wild-type," strain. By 27 weeks, the mutant-infected mice started to die, while their counterparts infected with the wild-type strain survived until the end of the experiment at 41 weeks.

"These findings came as a complete surprise to us," said Dr. Lee Riley, professor of epidemiology and infectious diseases at UC Berkeley's School of Public Health and principal investigator of the study. "We thought we had made a mistake, so we repeated the test several times, and we always got the same result."

The researchers say the study, to be published Dec. 8 in Proceedings of the National Academy of Sciences, sheds light on the mechanisms used by a pathogen that now infects one-third of the world's population and kills 2 million people per year. According to the World Health Organization, which in 1993 declared TB a global emergency, an estimated 36 million people could die of TB by 2020 if the disease is not controlled.

The results were unexpected because prior studies pointed to the mce1 operon, the collection of genes that researchers disabled in the TB bacteria, as an important virulence factor that helped the organism invade cells. Researchers expected that mutating the mce1 genes would impair the pathogen's ability to infect the mice. Instead, the bacteria became more deadly.

"This is one of the very few hypervirulent organisms ever created," said Lisa Morici, a lead author of the study who received her Ph.D. in in
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Contact: Sarah Yang
scy@pa.urel.berkeley.edu
510-643-7741
University of California - Berkeley
8-Dec-2003


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