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Scientists at Harvard Medical School have discovered a new family of proteins that almost all bacteria use to build and maintain cell walls.
Research leaders David Rudner and Thomas Bernhardt said finding a second group of cell wall synthesizers could help pave the way for the development of much-needed therapies to target cell walls as a way to kill harmful bacteria.
The findings were published in the August 15 issue of Nature.
Rudner, a senior author of the paper and a professor of microbiology and immunobiology at Harvard Medical School, said: "We know that these proteins are excellent targets because we can inhibit these enzymes from the outside of the cell."
Bernhardt, a co-author of the paper and a professor of microbiology and immunobiology at Harvard Medical School, said: "Now we have a better understanding of the function of these proteins and how a potential drug might affect their activity."
The cell wall plays a vital role in maintaining the structural integrity of the bacteria, determining its shape, and resisting external attacks from toxins, drugs, and viruses. The cell wall is composed of sugar chains that are joined together by short peptides.
For half a century, it has been thought that penicillin-binding proteins are dominant and may be the only cell wall synthesizers.
Penicillin was discovered in 1928 and was first used to treat bacterial infections in 1942. However, it was not until 1957 that scientists understood the mechanism by which penicillin blocked the construction of these proteins in bacterial cell walls. The study of E. coli in the 1970s and 1980s elaborated on the mechanism by which penicillin-binding proteins construct cell walls.
Later clues suggest that other factors may be involved in cell wall biosynthesis. In 2003, an important research finding that was overlooked by many people in the field was found: in the absence of penicillin-binding proteins, Bacillus subtilis was able to grow and synthesize its cell walls. Some researchers are very interested in this "missing polymerase", sometimes called "part-time enzyme."
The co-author of the paper, Tsuyoshi Uehara, a former researcher at the Bernhardt Laboratory at Harvard Medical School, believes that a family of proteins responsible for cell shape, elongation, division and sporulation: SEDS protein may be the main suspect for this missing enzyme. SEDS moves along the periphery of bacterial cells in a way that they may be involved in the synthesis of cell walls, which, if inactivated, disrupt cell wall synthesis.
To verify that the SEDS protein may be involved in cell wall synthesis, the first author of the paper, Alexander Meeske, a graduate student at Rudner Laboratories, Harvard Medical School, removed all known penicillin-binding proteins involved in the polymerized cell wall. The SEDS protein continues to move in much the same way as before. Observations have made the SEDS protein look like a missing enzyme, and more like a major factor than a part-time. Subsequent genetic and biochemical experiments confirmed that the SEDS protein is indeed a brand new family of cell wall synthesizers.
The scientists also found that two families of cell wall synthesizers work together: the SEDS protein creates a hoop-like structure around the cell wall, and the penicillin-binding protein moves in a dispersed manner, forming a smaller structure that is constructed with the hoop-like structure. Out of the cell wall.
Researchers say earlier studies have shown that bacteria can die when blocking penicillin-binding proteins, masking the importance of SEDS proteins.
In the current paper, scientists have found that SEDS proteins are more common in bacteria than penicillin-binding proteins, which gives us hope that a potential antibiotic that targets SEDS proteins can effectively fight a broad spectrum of bacteria.
Bernhardt said: "For a long time, in this field, people think that a group of enzymes work in a group of complexes to build a wall. Now we have two sets of enzymes that seem to work in different systems. I don't know. Fortunately, they must coordinate the construction of this network to maintain integrity and expand as cells grow and divide."
Nature Subversion of Biological Dogma: The Second Group of Cell Wall Synthesizers
[China Pharmaceutical Network Technology News] For half a century, people think that penicillin-binding protein is the main, and may be the only cell wall synthesizer. But researchers at Harvard Medical School recently discovered a second group of cell wall synthesizers that could help pave the way for the development of much-needed therapies to target cell walls as a way to kill harmful bacteria.
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