By examining decades' worth of stored bacteria samples, researchers have determined how a benign organism evolved into a deadly pathogen that causes necrotizing fasciitis, commonly known as flesh-eating bacteria disease.
Using genetic sequences from more than 3,600 strains of bacteria, scientists were able to see that it took only four steps to create the unusual microbe that spreads rapidly and destroys the body's soft tissue. Their report was published Monday in the Proceedings of the National Academy of Sciences.
Necrotizing fasciitis is caused by several types of bacteria, most commonly group A Streptococcus. (See images of Streptococcus and other microbes in the "Small, Small World" photo gallery.) An international group of researchers sequenced the genomes of group A strep bacteria in samples that had been collected from as early as the 1920s. Those sequences revealed that sometime in the past, group A strep was infected with first one virus and then soon after with another. With each infection, the bacterium gained viral genes that made group A strep more likely to cause disease.
"The third event was a mutation of a single letter of the genome of the organism to create an even more virulent form," said the study's main author, James Musser, director of the Center for Molecular and Translational Human Infectious Diseases Research at the Houston Methodist Research Institute in Texas. That mutation probably occurred in the late 1960s.
Then, in the early 1980s, the bacterium acquired another piece of foreign DNA, which carried the code for two toxins that cause necrotizing fasciitis's worst effects. "We were off and running with a strain that had increased ability to spread in humans and to cause a more severe form of disease," Musser said.
A Long Search for Answers
The new research would not have been possible without the foresight of several international collaborators who saved comprehensive samples of this kind of bacteria for many decades. That let scientists study how the organism evolved over all that time.
"If you simply sequenced the samples from today, you really wouldn't understand how and when it flipped from a bad pathogen to a really bad pathogen," Musser said.
Musser has been gripped with curiosity about the flesh-eating disease since Muppets creator Jim Henson died of the infection in 1990. At that time a new field of research—bacterial population genetics—was just beginning. "This has been my white whale for almost 25 years," Musser said.
Today about 650 to 800 Americans become infected with flesh-eating bacteria each year, according to the Centers for Disease Control and Prevention. The bacteria infect layers of membranes and connective tissue around muscle, nerves, fat, and blood vessels. The toxins made by the bacteria destroy the tissue they infect, causing it to die.
Healthy people with strong immune systems who carefully clean and care for cuts, scrapes, and insect bites are usually able to fight off the bacteria. But people with compromised immune systems or with conditions such as diabetes, kidney disease, or cancer are more vulnerable.
Jacqueline Roemmele was one such unlucky person. She became infected in 1994 after the cesarean section birth of her twins. "Before they found what it was, my flesh was falling off in the nurses' hands," she said. Roemmele survived and went on to found, with Donna Batdorff, the National Necrotizing Fasciitis Foundation.
The new discovery "is very exciting," Roemmele said. "This is the first time I've heard of science ripping apart how this actually happens to explain: Why did this become a supercharged bacteria? ...This gives us greater insight into why it happens."
There is still a lot of work that needs to be done toward finding methods to prevent, treat, and cure necrotizing fasciitis. But this study shows that analyzing the timing of the molecular events that lead to global epidemics can help to monitor and predict the emergence of deadly infectious diseases.
"This is the first time we've been able to sort out the precise events that give rise to bacterial epidemics," said Musser. "We need to understand the general rules in order to understand epidemics. This is the first understanding of that."