Scientists have identified a new family of proteins that virtually all bacteria use to build and maintain their cell walls. The discovery of a second set of cell wall synthesizers may inform development of much-needed antibacterial therapies, say study leaders David Rudner and Thomas Bernhardt, both professors in the HMS Department of Microbiology and Immunobiology. Their research team reported its work online on August 15 in Nature.
Made up of chains of sugars linked by short peptides, a bacterium’s cell wall plays a critical role in maintaining its structural integrity, dictating its shape, and repelling external assaults from toxins, drugs, and viruses.
Penicillin-binding proteins—molecules named for the drug that disables them—were long thought to be the major, perhaps only, cell wall synthesizers. The fact that these proteins were integral to cell wall construction was revealed in the late 1950s, but the mechanism behind their action was not unraveled until the 1970s and 1980s in research using the bacterium Escherichia coli.
Clues that other players may be involved in cell wall biogenesis emerged later. Tsuyoshi Uehara, a former HMS research fellow in the Bernhardt lab and co-author of the paper, thought a family of proteins responsible for a cell’s shape, elongation, division, and spore formation—SEDS proteins in scientific shorthand—could be an unidentified player.
SEDS proteins move around the circumference of the bacterial cell. If the proteins are inactivated, cell wall synthesis is perturbed.
In genetic and biochemical experiments, the research team confirmed that SEDS proteins were a new family of cell wall synthesizers that behaved in a different yet complementary way from the penicillin-binding proteins. SEDS proteins circumnavigate the cell wall, making hoop-like structures, while penicillin-binding proteins move diffusely, making smaller strands that, together with the hoop-like strands, build the cell wall.
In the current paper, the scientists found that SEDS proteins are more common in bacteria than are the penicillin-binding proteins, raising hopes that a potential antibiotic targeting SEDS proteins could be effective against a broad spectrum of bacteria.
Image: Rudner lab