Bringing Down the Wall

The first detailed images of an elusive drug target on the outer wall of bacteria may provide scientists with enough new information to aid design of novel antibiotics. The drugs are much needed to treat deadly infections initiated by Staphylococcus aureus and other bacterial pathogens.

Penicillin and many newer antibiotics work by blocking a piece of the machinery bacteria use to construct their durable outer walls. Without these tough, protective coatings, bacteria die. The enzymatic machinery (known as PBP2) studied by researchers has two main parts: One end assembles long sugar fibers; the other end stitches them together with bits of protein to form a sturdy interlocking mesh shell.

The research team has provided a long-awaited look at the portion of the enzyme used in the first step of the biochemical pathway that initiates assembly of the sugar coating. The second step is targeted by penicillin and has been well studied.

The images produced show the enzyme frozen in place by a powerful antibiotic called moenomycin. Moenomycin has been used for decades in animal feed to promote livestock growth. Bacteria have shown very little evidence of resistance to this antibiotic so far, and scientists think related compounds may be promising candidates for use in humans.

"This enzyme is an awesome target for antibiotics," said Natalie C.J. Strynadka, a researcher from Howard Hughes Medical Institute. "We have a totally new understanding of how the enzyme works and how a very good animal antibiotic inhibits the enzyme." Although moenomycin is poorly absorbed by the human body, the new understanding of exactly how it interferes with bacterial enzyme function should help scientists design modified versions that are more suitable for use in people.

---LiveScience Staff

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Credit: Natalie Strynadka