"We identified a biochemical process that uses a previously unrecognized molecule as a raw material to make phospholipid," Rock said. "That discovery solved a mystery that has puzzled researchers for 25 years."
Scientists have used E. coli bacteria for many years as a model to understand how disease-causing bacteria make membrane phospholipids, but E. coli is an unsuitable model for most pathogens (disease-causing bacteria), according to Rock.
First, E. coli is a so-called gram-negative bacterium, while many of the pathogens researchers are interested in are gram-positive, Rock noted. Among those gram-positive organisms are Staphylococcus aureus, which causes skin infections and serious blood infections, and Streptococcus pneumoniae, which causes pneumonia. The terms "gram-positive" and "gram-negative" refer to the response of bacteria to a standard laboratory process by which they are stained as a first step in identification.
Laboratory strains of E. coli do not cause disease; and the enzyme E. coli uses during the first step in making membranes does not exist in most other bacteria, including gram-positive pathogens. Therefore, the way gram-positive bacteria make phospholipid building blocks remained a mystery for over more than two decades. Now, however, the St. Jude team reports that the gram-positive pathogens use two enzymes, called PlsX and PlsY, to kick off phospholipid synthesis.
"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 the St. Jude Department of Infectious Diseases. "It turns out that E. coli is more of an oddball rather than in the mainstream when it comes to how it makes membranes."
E. coli fuses a molecule called G3P with a fatty acid in a single step. Rock's team showed that gram-positive pathogens first use PlsX to synthesize a compound called fatty acyl-phosphate, then use PlsY to transfer the fatty acid to G3P. These steps initiate membrane phospholipid formation required for cell growth.
"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."
Source: Newswise
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