The study, conducted by an international team led by RML scientist James M. Musser, M.D., Ph.D., will appear in the Proceedings of the National Academy of Sciences online sometime this week.
"This work indicates that using extensive genome-wide molecular analyses is an important new strategy for understanding how and why pathogens emerge," notes NIAID Director Anthony S. Fauci, M.D. "What's more, the method can be applied to other bacterial and viral pathogens by adjusting the techniques and strategies."
Previous studies, Dr. Musser says, substantially underestimated genetic diversity in bacteria because these studies neither employed the array of molecular techniques they did nor analyzed a comprehensive database of patient samples.
"Before the advent of genome sequencing and genome-wide analysis methods, our knowledge of molecular characteristics of pathogenic bacterial infections in distinct populations was extremely limited," says Dr. Musser.
In the new study, the RML team identified previously unknown genetic distinctions in M3 strains of GAS, revealing why only some strains rapidly expand to cause epidemics. All GAS strains can cause serious infections, Dr. Musser says, but the M3 strains are unusually virulent.
Dr. Musser explains that shortly after 2002, when he and his colleague Stephen Beres, Ph.D., at RML completed a genome sequence of the serotype M3 GAS, they turned their attention to using the new information to molecularly dissect two epidemics of life-threatening GAS infections, or necrotizing fasciitis--the "flesh-eating" syndrome. The study involved analyzing hundreds of patient cultures obtained over 11 years from Ontario, Canada, in epidemiologic studies conducted by Donald Low, M.D., and Allison McGeer, M.D., of the Mount Sinai Hospital in Toronto.
"We proposed an extensive collaboration that would mesh the RML GAS genomic analysis information with the Ontario patient samples and epidemiologic information to provide new understanding of these two GAS epidemics," Dr. Musser says. The Baylor College of Medicine in Houston, with which Dr. Musser is also affiliated, also contributed to the project.
Dr. Musser's team analyzed a comprehensive sample of GAS cultures collected from patients between 1992 and 2002. Using the new genetic tools, the team discovered previously unknown genetic shifting and the evolution of new M3 strains, particularly in the peak epidemic years of 1995 and 2000. For the first time, scientists were able to unravel, on a genome-wide basis, the complex molecular events underpinning the emergence of new epidemic waves of bacterial infection.
The discoveries should help scientists develop better ways to control GAS infection, including vaccine development and new therapies. GAS infections can range from mild skin infection or strep throat to invasive, life-threatening conditions such as toxic shock syndrome and necrotizing fasciitis. Strep throat, along with minor skin infections, are the most common forms of the disease.
Experts estimate that more than 10 million GAS infections occur every year in the United States. In addition, according to the Centers for Disease Control and Prevention, 9,000 cases of severe GAS disease were reported in 2002.
NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
Note: Media may request a copy of the paper by calling the National Academy of Sciences at 202-334-1310. Ask for manuscript number 04-04163.
Reference: S Beres et al. Genome-wide molecular dissection of serotype M3 Group A Streptococcus strains causing two epidemics of invasive infections. Proceedings of the National Academy of Sciences DOI:10.1073/PNAS.0404163101.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Journal
Proceedings of the National Academy of Sciences