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    Charles O. Rock, PhD

    Solution to bacterial mystery promises new drugs

    A 25-year quest to identify the first biochemical step that many disease-causing bacteria use to build their membranes has led to a discovery that holds promise for effective, new antibiotics against these same bacteria, according to St. Jude investigators. The finding is significant because the biochemical step such an antibiotic would block is not used by humans, which suggests that such a drug would not cause dangerous side effects.

    A report on this finding appears in the September 1 issue of Molecular Cell.

    The discovery also demonstrated that current textbooks use the wrong type of bacterium as a model to explain the critical first biochemical step that most disease-ausing bacteria use to make phospholipids—the building blocks of membranes, according to Charles Rock, PhD, Infectious Diseases.

    Scientists have used E. coli bacteria for many years as a model to understand how most disease-ausing bacteria of a type called “gram-positive” make membrane phospholipids, Rock said. But E. coli, a “gram-negative” bacterium, turns out not to be a suitable model for most pathogens.

    The St. Jude team reported that, while it has long been known that E. coli uses the enzyme PlsB to kick off phospholipids synthesis, the gram-positive disease-causing bacteria use two enzymes, called PlsX and PlsY.

    “In fact, the biochemical pathway that uses PlsX and PlsY is the most widely distributed bacterial pathway for initiating the production of phospholipids,” explained Ying-Jie Lu, PhD, Infectious Diseases, the study’s first author.

    “Our discovery of PlsX and PlsY not only solved a troublesome mystery,” Rock said. “It’s also important because identifying the essential components required for disease-causing bacteria to grow and multiply is a key part of developing new strategies for controlling infections.”

    The other St. Jude author of the study is Yong-Mei Zhang, PhD, Infectious Diseases.


    October 2006