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Thursday, Feb. 3, 2005
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.
View an image of PGA clusters on S. epidermidis
###References: 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). DOI: 10.1172/JCI200523523
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). DOI: 10.1172/JCI200523523
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Last Updated February 03, 2005