Staphylococcus Epidermidis

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.

Staph 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., appeared in the March edition of The Journal of Clinical Investigation. 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 healthcare 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 strain - 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.

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.

Staph Epidermidis is capable of clinging to tubing (as in that used for intravenous feeding, etc.), prosthetic devices, and other non-living surfaces, S. Epidermidis is the organism that most often contaminates devices that provide direct access to the bloodstream. The primary cause of bacteremia in hospital patients, this strain of Staph is most likely to infect those, whose immune systems have been compromised for any reason, and high-risk newborns receiving intravenous supplements.

S. Epidermidis also accounts for two of every five cases of prosthetic valve endocarditis. Prosthetic valve endocarditis is endocarditis as a complication of the implantation of an artificial valve in the heart. Although contamination usually occurs during surgery, symptoms of infection may not become evident until a year after the operation. More than half of the patients who develop prosthetic valve endocarditis die.

Staphylococcus Epidermidis, which is a common bacteria in the nipple ducts, is thought by some doctors to cause a subclinical infection and perhaps cause capsule contracture.

When the patient has few clinical signs except severe pain it suggests that the bacteria may be pseudomonas. This bacteria seems to irritate nerve endings more than other germs. Another rare infection is caused by mycobacterium fortuitum. This causes inflammation around the implant but no symptoms in other parts of the body. Patients do notusually have a raised temperature but about one in three have drainage from the surgical site.

Staph Epidermidis is a common member of the normal florae of skin and mucous membranes. Its large numbers and ubiquitous distribution make it one of the most commonly isolated organisms in the clinical laboratory. While at one time the appearance of S. Epidermidis in clinical material could be dismissed as contamination, it is now one of the most important agents of hospital acquired infections. Immunosuppressed or neutropenic patients are particularly at risk, as are individuals with indwelling catheters or prosthetic devices. It can also cause endocarditis in individuals with previous heart valve damage. The hydrophobic nature of the organism's cell surface facilitates its adherence to synthetic devices as well as damaged heart valves. Following initial colonization, a copious amount of extracellular polysaccharide or slime is synthesized, forming a protective biofilm around the colony. Because many isolates are multiply antibiotic resistant, these infections are very serious and can even be fatal.

Interestingly, Staph Epidermidis is normally resident in the skin flora, the gut and upper respiratory tract. It is a true opportunistic pathogen, requiring a major breach in the host's infection to establish infection, and invariably is hospital acquired. It is associated with skin penetration by implanted prostheses, for example Spitz Holter valves used to treat hydrocephalus, prosthetic heart valves, IV lines, intraperitoneal catheters and orthopaedic prostheses. It is a major cause of bacteraemia in neutropenics and in all infections there is a risk of endocarditis. It is also a serious neonatal infection, particularly in very low birth weight infants.

Staph Epidermidis produces some toxins but their significance is unknown. Adherence to a foreign surface is facilitated by the production of a viscous extracellular (proteoglycans) slime. Staph Epidermidis is coagulase negative.

This is a review of the biological properties of Staphylococcus Epidermidis describing its ability to colonise polymers and to form biofilms thus leading to chronicity of infection. It is known that capsular contraction after silicone breast implantation may be caused by chronic infection and the review supports the IRG's concern that low grade infection with an organism such as Staph Epidermidis could cause chronic ill health in some women who have had a breast implant.

Staphylococci are common causes of infections associated with indwelling medical devices. These are difficult to treat with antibiotics alone and often require removal of the device. Some strains that infect hospitalized patients are resistant to most of the antibiotics used to treat infections, Vancomycin being the only remaining drug to which resistance has not developed.