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 infections 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 new treatments 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. epidermidis 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 compounds 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
PGA did.
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