|Studies Highlight MRSA Evolution and Resilience
Community-associated methicillin-resistant Staphylococcus
aureus (CA-MRSA) infections are caused primarily by a single
strain — USA300 — of an evolving bacterium that has
spread with "extraordinary transmissibility" throughout
the United States during the past five years, according to a
new study led by National Institutes of Health (NIH) scientists.
CA-MRSA, an emerging public health concern, typically causes
readily treatable soft-tissue infections such as boils, but also
can lead to life-threatening conditions that are difficult to
The study, from the National Institute of Allergy and Infectious
Diseases (NIAID) of NIH, resolves debate about the molecular evolution
of CA-MRSA in the United States. The findings rule out the previously
held possibility that multiple strains of USA300, the most troublesome
type of CA-MRSA in the United States, emerged randomly with similar
characteristics. The study also offers a hypothesis for the origin
of previous S. aureus outbreaks, such as those caused
by penicillin-resistant strains in the 1950s and 1960s.
A second study led by the same NIAID scientists takes the issue
of the evolution of MRSA a step further, revealing new information
about how MRSA bacteria in general, including the USA300 group,
elude the human immune system.
The first study, which appears online this week in the Proceedings
of the National Academy of Sciences, found that the USA300
group of CA-MRSA strains, collectively called the epidemic strain,
comprises nearly identical clones that have emerged from a single
bacterial strain. It is the first time scientists have used comparative
genome sequencing to reveal the origins of epidemic CA-MRSA.
Frank R. DeLeo, Ph.D., at NIAID's Rocky Mountain Laboratories
(RML) in Hamilton, Mont., led the research.
"Scientists are pressing ahead quickly to learn more about
how some MRSA strains evade the immune system and spread rapidly," says
NIAID Director Anthony S. Fauci, M.D. "The information presented
in these two studies adds important new insights to that expanding
To understand how CA-MRSA is evolving in complexity and spreading
geographically, Dr. DeLeo's group sequenced the genomes of 10 patient
samples of the USA300 bacterium recovered from individuals treated
at different U.S. locations between 2002 and 2005. They then compared
these genomes to each other and to a baseline USA300 strain used
in earlier studies. Eight of the 10 USA300 patient samples were
found to have nearly indistinguishable genomes, indicating they
originated from a common strain. The remaining two bacteria were
related to the other eight, but more distantly.
Interestingly, of the eight nearly indistinguishable USA300 patient
samples, two caused far fewer deaths in laboratory mice than the
others, highlighting an emerging view that tiny genetic changes
among evolving strains can profoundly affect disease severity and
the potential for drug resistance to develop.
"The USA300 group of strains appears to have extraordinary
transmissibility and fitness," says Dr. DeLeo. "We anticipate
that new USA300 derivatives will emerge within the next several
years and that these strains will have a wide range of disease-causing
potential." Ultimately, Dr. DeLeo and his colleagues hope
that the work will lead to the development of new diagnostic tests
that can quickly identify specific strains of MRSA.
Fred C. Tenover, Ph.D., of the Centers for Disease Control and
Prevention in Atlanta (CDC) contributed the 10 USA300 clinical
isolates from CDC's Active Bacterial Core Surveillance system.
Other study collaborators included Barry N. Kreiswirth, Ph.D.,
of the International Center for Public Health (ICPH) in Newark,
N.J., and James M. Musser, M.D., Ph.D., of The Methodist Hospital
Research Institute in Houston.
The second report, which involved scientists from RML, ICPH and
Vanderbilt University Medical Center in Nashville, was recently
published online in the Journal of Immunology. This study
provides scientists with new details about the complex mechanisms
MRSA uses to avoid destruction by neutrophils, human white blood
cells that ingest and destroy microbes. When exposed to hydrogen
peroxide, hypochlorous acid (the active component of household
bleach) or antimicrobial proteins — all killer chemicals
released by neutrophils — MRSA senses danger, escapes harm
and turns the tables on the white blood cells, destroying them.
Work is continuing in Dr. DeLeo's lab to understand how the bacterium
senses and survives attacks by neutrophils.
NIAID is a component of the National Institutes of Health. 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 basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies.
News releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
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its programs, visit www.nih.gov.
A Kennedy et al. Epidemic community-associated methicillin-resistant Staphylococcus
aureus: Recent clonal expansion and diversification. Proceedings
of the National Academy of Sciences DOI:10.1073/PNAS.0710217105
A Palazzolo-Ballance et al. Neutrophil microbicides induce
a pathogen survival response in community-associated methicillin-resistant Staphylococcus
aureus. The Journal of Immunology (2008) 180:500-509.