GenomeWide Analysis Provides Detailed Understanding of FleshEating Bacteria Epidemics
New research using nearly a dozen different genomic testing procedures
has revealed unprecedented detail about the molecular characteristics
and virulence of group A streptococcus (GAS), the "flesh-eating"
bacteria, according to scientists at the Rocky Mountain Laboratories
(RML), part of the National Institute of Allergy and Infectious
Diseases (NIAID) of the National Institutes of Health.
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
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.
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.