Flippase Finally Found

Scientists now have convincing evidence that the inner cell membrane protein MurJ is the long-sought-after flippase. This enzyme is known to be essential to forming bacterial cell walls and represents a target for developing new antibiotics. MurJ has been one of a few strong suspects as the protein that transports, or flips, peptidoglycan precursors from inside the cell’s cytoplasm where they’re formed to the outer regions where they combine to form tough cell walls. Although current antibiotics interfere with various stages of bacterial peptidoglycan-forming processes, scientists would like to be able to develop new drugs by targeting flippase. A team led by Natividad Ruiz of Ohio State University and Thomas G. Bernhardt of Harvard Medical School developed a method for monitoring flippase activity in the sometimes pernicious bacterium Escherichia coli (Science 2014, DOI: 10.1126/science.1254522). When the group inactivated MurJ in the bacteria, flippase activity dropped precipitously, strongly suggesting that MurJ is the mystery flipper.