| Substance Protects Resilient Staph Bacteria
Researchers have identified a promising new target in their fight
against a dangerous bacterium that sickens people in hospitals,
especially people who receive medical implants such as catheters,
artificial joints and heart valves.
A substance found on the surface of Staphylococcus epidermidis
has, for the first time, been shown to protect the harmful pathogen
from natural human defense mechanisms that would otherwise kill
the 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.
S. epidermidis is one of several hard-to-treat infectious
agents that can be transmitted to patients in hospitals via contaminated
medical implants. The new report concludes that the substance — known
as poly-gamma-DL-glutamic acid, or PGA — must be present
for S. epidermidis to survive on medical implants. S. epidermidis
are rarely fatal but can lead to serious conditions such as sepsis
(widespread toxic infection) and endocarditis (inflammation of
the lining of the heart and its valves).
Because of the ability of PGA to promote resistance to innate
immune defenses, learning more about the protein could lead to
for S. epidermidis and related Staphylococcal pathogens that also
produce PGA, according to the RML scientists. In addition, they
also are hoping that similar research under way elsewhere on Bacillus
anthracis — the infectious agent of anthrax, which also produces
PGA — will complement their work.
The report of the study, led by Michael Otto, Ph.D., will appear
in the March edition of The Journal of Clinical Investigation,
and is now available online. Collaborators, all scientists at RML
in Hamilton, MT, include Stanislava Kocianova, Ph.D.; Cuong Vuong,
Ph.D.; Yufeng Yao, Ph.D.; Jovanka Voyich, Ph.D.; Elizabeth Fischer,
M.A.; and Frank DeLeo, Ph.D.
“Nosocomial, or hospital-acquired, infections are a worrisome public
health problem made worse by the increase in antibiotic resistance,” says
NIAID Director Anthony S. Fauci, M.D. “This research has
initiated a promising new approach that could result in the development
of better ways to prevent the spread of many different staph infections
that can be acquired in health care settings.”
The PGA discoveries came during Dr. Otto’s research of how
Staphylococcal bacteria biofilms contribute to evading human immune
defenses. Biofilms are protective cell-surface structures. Biofilm
formation does not depend on PGA, but other research in Dr. Otto’s
laboratory has indicated that PGA production is greater when a
biofilm is present. Further, Dr. Otto says all 74 strains of S.
epidermidis that his group tested also produced PGA, as did six
other genetically related Staphylococcus pathogens. “This
could be very important to vaccine development because the PGA
is present in every strain of the organism,” Dr. Otto says. “If
a vaccine can be developed to negate the effect of the PGA, it
could be highly successful against all pathogens in which PGA is
a basis for disease development, such as Staph and anthrax.”
The group used genetic and biochemical analyses to show that
PGA is produced in S. epidermidis. They then used three S.
strains — one natural, one altered to eliminate PGA production
and one altered to produce excess PGA — to show that PGA
protects S. epidermidis from innate immune defense, human antibiotic
and salt concentrations similar to levels found on human skin.
Dr. Otto’s group also used mice fitted with catheters to
demonstrate that the S. epidermidis strain deficient of PGA was
not able to cause infection while the other strains containing
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. News releases, fact sheets and other NIAID-related materials
are available on the NIAID Web site at http://www.niaid.nih.gov.
Note: For an image of PGA clusters on S. epidermidis, see http://www.niaid.nih.gov/newsroom/Releases/S_epidermidis.htm
Reference: S. Kocianova et al. Key role of poly-gamma-DL-glutamic
acid in immune evasion and virulence of Staphylococcus epidermidis.
The Journal of Clinical Investigation (www.jci.org).