Nisin, and presumably geobacillin, work by binding to a molecule the pathogen needs to build its cell wall and then poking holes in the bacterial cell’s membrane, a one-two punch that quickly kills the invader. However, the two antibiotics have slight structural differences. Nisin’s structure has five looped regions, formed by cross-links in the protein chain. Geobacillin has seven loops thanks to two additional cross-links, which give the protein added stability.

The team tested geobacillin against several foodborne and disease-causing bacteria and found it similarly effective or more effective than nisin, depending on the bacteria. Most significantly, it was three times more active against the main contagious bacteria responsible for bovine mastitis. Contagious mastitis is devastating for dairy farmers, as the bacteria can quickly spread throughout a herd. In addition, since mastitis could be caused by a number of different infections, geobacillin’s broad-spectrum activity makes it a very attractive treatment option.

Next, the researchers plan to test geobacillin against a wider spectrum of disease-causing bacteria. Many tests of safety, efficacy and economic production lie ahead, although geobacillin has shown great promise in tests to date. The researchers hope that its greater stability will enable medicinal applications for geobacillin that nisin could not realize, both for bovine mastitis and possibly for human disease.

“Nisin was very promising in early preclinical trials in that it was very effective in killing multi-drug-resistant bacteria in mouse models,” said van der Donk, “but because of its instability, it has a very short half-life in blood. So we’re looking to see whether geobacillin has greater serum stability.”

The researchers published their findings in the Proceedings of the National Academy of Science. The National Institutes of Health supported this work. Van der Donk is also a Howard Hughes Medical Investigator.