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 bacteria, according to investigators at St. Jude Children's Research Hospital. The finding is significant because the biochemical step such an antibiotic would block is not used by humans. Therefore, 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-causing bacteria use to make phospholipids-the building
blocks of membranes, according to Charles Rock, Ph.D., a member of the St. Jude Department of Infectious Diseases and senior author of the paper.


Scientists have used E. coli bacteria for many years as a model to
understand how disease-causing bacteria make membrane phospholipids. But E. coli, a "gram-negative" bacterium, is an unsuitable model for most disease- causing bacteria, Rock said.


The St. Jude team reported that, while it has long been known that E.
coli uses the enzyme PlsB to kick off phospholipids synthesis,
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 the study's first author, Ying-Jie Lu, Ph.D., of
St. Jude.


"Our discovery is 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," Rock
said.


Other authors of the study include Yong-Mei Zhang (St. Jude) and
Kimberly Grimes, Jianjun Qi and Richard Lee (University of Tennessee).


This work was supported in part by the National Institutes of Health, a
Cancer Center (CORE) Grant, and ALSAC.


St. Jude Children's Research Hospital


St. Jude Children's Research Hospital is internationally recognized for
its pioneering work in finding cures and saving children with cancer and
other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with
scientific and medical communities around the world. No family ever pays
for treatments not covered by insurance, and families without insurance are
never asked to pay. St. Jude is financially supported by ALSAC, its
fund-raising organization. For more information, please visit
stjude.


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