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New method may speed identification of antibiotic targets

Which DNA is essential for life?

Stanford researchers have developed a streamlined new genetic analysis that answered that question for one bacterial species, Caulobacter crescentus. The team found that 12 percent of the bacterial DNA is needed for survival in lab conditions, including many familiar genes and some nucleotide sequences of mysterious function. The findings appear today in Molecular Systems Biology.

The research holds perhaps its greatest potential as a tool for finding metabolic weaknesses in pathogenic bacteria - which, unlike Caulobacter crescentus, can make us sick. Our press release describes that potential:

The scientists also pointed out that the method could be used to examine which DNA segments are essential for bacterial survival in specific circumstances, such as when pathogenic bacteria invade a host animal or plant. Developing a comprehensive list of genetic elements that make a bacterial species infectious could lead to the identification of new anti-infective agents including new antibiotics.

One big stumbling block in antibiotic development today is that researchers struggle to judge where bacteria are vulnerable to drugs' attacks. Ideally, an antibiotic should shut down a metabolic process that is essential for bacterial survival (to kill the bug); non-existent in humans (to prevent drug side effects); and easy to disrupt chemically. Having a list of all essential parts of a bacteria's DNA would give a big boost to scientists trying to identify drug targets that meet all three criteria.

"It's a comprehensive approach, as opposed to poking here and there, which is what we do now," said Lucy Shapiro, PhD, who led the research team. "Lots of surprises will come out of that."

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