The flipping protein found at last?

US researchers believe they have answered the last major question in the effort to understand the pathway that leads to the creation of a bacterium’s cell wall. It is possible that their breakthrough could help lead to the wall’s destruction and, with it, the eradication of various types of bacterial infection.

A polymer called peptidoglycan (PG) forms the cell wall of most bacteria. To create this wall, bacteria make PG precursors deep in their cytoplasm, attach them to a lipid carrier (lipid II) and transport (flip) them across the cytoplasmic membrane, where the building blocks are woven into the developing cell wall structure.

The enzymes that help in this process are well known, but scientists have so far been unable to identify the flippase that helps the precursors cross the nearly impenetrable cytoplasmic membrane. A team led by Lok-To Sham devised a technique to assay the flippase’s in vivo activity, a deed that was until now impossible. The researchers explained that they “developed an assay for lipid II flippase activity and used a chemical genetic strategy to rapidly and specifically block flippase function”.

The findings, published in the journal Science, demonstrate that a protein called MurJ performs the flippase function in E.coli. But while the work appears to solve a major puzzle in the basic pathway that synthesises the bacterial cell wall, a piece by Kevin D Young, also published in Science, notes that “in vitro experiments identified another candidate, FtsW, as the relevant flippase, with MurJ being inactive”.

If the protein can in fact be confirmed for certain, it will help provide an attractive target for new antibiotics.

Source: Science/AAAS.