The mid-1980s saw the emergence of a severe new type of invasive, flesh-eating bacterial infection, sometimes called necrotizing fasciitis, which could rapidly kill a person or cost them a limb. These infections, which currently number several hundred per year in the U.S., are caused by one of several juiced up varieties of Group A Streptococcus, the same bacterium that causes millions of cases of strep throat and other minor infections annually. In 2002 Musser and his colleague sequenced the genome of one of the most pernicious of these flesh eaters, the Group A strain M3. They found that the strain had acquired the gene for phospholipase A2, called SlaA, in the mid-1980s, which suggested that SlaA was responsible for the jump in virulence. How the enzyme might have helped the bacterium thrive was unknown, though.
In a report published online October 16 in Proceedings of the National Academy of Sciences USA, Musser's group details some of SlaA's advantages. The researchers compared the usual M3 strain, containing SlaA, with a mutant version lacking the enzyme. Whereas mice infected with the regular M3 died within a day, a quarter of animals infected with the mutant form survived. Similarly, monkeys exposed to the normal strain contained thousands of times more bacteria in their throats than those given the mutant version. The regular bacteria were also better able to stick to cultured human cells. Considering the wild strain's greater numbers and increased severity, "it's actually a two-for-one strategy that the organism gets with this toxin," Musser says. "It's quite a clever toxin in that regard."
Although the group didn't identify the toxin's target, it probably causes cells to die from within by overstimulating the immune system, says immunologist Harry Hill of the University of Utah. Similar to another phospholipase toxin, SlaA produces a fatty acid that contributes to inflammation. "I think a lot of the damage is caused by vastly enhancing and promoting this inflammatory response," says Hill.