Armed with genome maps, researchers have gained a critical insight into why a particular strain of a common bacterium causes rheumatic fever--the leading cause of preventable childhood heart disease. It turns out the strain is the victim of an attack itself--infiltrated by viruses that inserted DNA for the toxins that stoke the deadly fever.
Rheumatic fever outbreaks are associated with so-called M18 strains of Streptococcus bacteria. Cases start like strep throat. But, unlike the Streptococcus strains that cause strep throat, M18 strains aren't killed by penicillin. If the infection isn't stopped, it can progress into rheumatic fever--a highly contagious disease that affects more than 400,000 people worldwide each year and leaves survivors with lasting damage to heart valves and other tissue.
Doctors can't predict who will contract the disease, in part because strep tests don't distinguish between M18 and other strains.
Determined to explain why M18 strains are so virulent, physician and microbiologist James Musser--along with colleagues from the National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories in Hamilton, Montana--took a broad look at M18 strains. They mapped the genomes of 36 strains collected from patients who died in rheumatic fever outbreaks across the U.S. in the last 73 years. When the team laid out the genome maps side by side, they were amazed to discover that the M18 strains were virtually identical. Moreover, 90% of the genetic difference between the M18 and streptococcal strains that don't cause rheumatic fever is due to chunks of genetic code inserted into the bacteria's DNA by phages, viruses that infect bacteria. So the team reports in a paper published online 26 March in the Proceedings of the National Academy of Sciences.
The team found that the phage-inserted genetic codes carry instructions for tissue-damaging toxins, including two that were previously unknown.
"Streptococcus is a challenging bacteria to work with because it has so many different strains," says Patrick Schlievert, a microbiologist at the University of Minnesota, Twin Cities. Until now, he says, researchers have been at a loss to explain what makes some strains more virulent than others. But this study provides the "solid base" of knowledge that researchers need. Now, says Schlievert, they can work more effectively to develop new diagnostic tests for detecting the M18 strain bacteria and vaccines designed to disable its toxins.