Somewhere along its evolutionary path, a benign microorganism turned into the virulent pathogen that causes necrotizing fasciitis, the “flesh-eating” infection. Despite its name, the bacteria don’t actually eat flesh, rather, they destroy the body’s soft tissue by producing proteins that break down skin, fat, and muscle. And after decades of research, scientists haven’t been able to agree on the genomic alternations that grew into this ongoing, global epidemic.
Now, after conducting one of the biggest bacterial genome analyses ever, researchers have pinpointed the nature and timing of key molecular events that caused the drastic switch – which they say occurred in the early 1980s.
A team led by James Musser of Houston Methodist Research Institute sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus, the flesh-eating bacteria. “We needed this magnitude of data," Musser tells the Verge, "to be clear about what transpired to create this thug pathogen."
By coupling that with animal virulence studies, the team traced the pathogen’s origin to a single progenitor cell line. The progenitor -- which first produced a virulence factor -- evolved through a series of steps until 1983, when it acquired the genes responsible for producing two toxins that cause the devastating effects of necrotizing fasciitis. The acquisition of these genes was the final major event preceding the pathogen’s emergence and transition to a global epidemic.
Working backwards, they discovered four key genetic changes. Some time before the 1960s, two mutations arose when the single precursor cell became infected with two different types of viruses. “Bacteria, just like humans, can get infected by viruses,” Musser tells Wired. Through a common process called horizontal gene transfer, bacteria-infecting viruses (bacteriophages) can transfer their genetic material to bacteria, which then incorporate the foreign DNA into their genome. Those phages encode for the SdaD2 virulence factor and SpeA1 toxin. A further mutation in the 1960s or 70s made one of the toxin genes even more virulent, resulting in the SpeA2 toxin. And finally, around 1983, another horizontal gene transfer event gave the bacteria the ability to encode the two toxins in massive quantities.
"Over time, there was a cell that sequentially acquired these various additional parts so that at the end of the day, when it acquired that fourth event, it created that souped-up streptococcus,” Musser says. Not only does it have the ability to cause an increased number of infections, it can also increase the severity of infection, he adds.
That date sounds about right: Since 1983, there have been several outbreaks across the world. The researchers hope their findings will help nip epidemics in the bud, or at least help tailor drug research.
The work was published in Proceedings of the National Academy of Sciences this week.
Image: CDC/ Melissa Brower via Public Health Image Library