Substance protects resilient Staph bacteria
fight against resilient Staphylococcus bacteria that can be
transmitted to patients in hospitals via contaminated medical
implants.
This achievement is all the more important as researchers look towards a new generation of antimicrobial compounds designed to target the bacteria's natural defences. The target is a substance found on the surface of Staphylococcus epidermis has, for the first time, been shown to protect the harmful pathogen from natural defence mechanisms that would otherwise kill the bacteria.
S. epidermidis is one of several hard-to-treat infectious agents that can be transmitted to patients in hospitals. The substance, known as poly-gamma-DL-glutamic acid (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 defences, the protein target could lead to new treatments for S. epidermidis and related Staphylococcal pathogens that also produce PGA. In addition similar research under way on Bacillus anthracis, the infectious agent of anthrax, also produces PGA is set to yield similar results.
"Nosocomial infections are a worrisome public health problem made worse by the increase in antibiotic resistance," says NIAID director Anthony Fauci.
"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 acquired in health care settings," he added.
The emergence of Staphylococcus infections is an additional threat to the public health crisis of antimicrobial resistance. Efforts to control these types of infections can no longer depend solely on surveillance, infection control efforts, and judicious antibiotic prescribing practices within the hospital setting.
Proactive patient education, aggressive diagnostic efforts, and effective treatment for infections by outpatient clinicians, will not only improve patient care, but also protect communities and hospitals from an increasingly prevalent pathogen.
The PGA discoveries came during research of how Staphylococcal bacteria biofilms contribute to evading human immune defences. Biofilms are protective cell-surface structures and while formation does not depend on PGA, other research indicated that PGA production is greater when a biofilm is present.
Dr Michael Otto, lead researcher of the study said: "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."
Otto said that all 74 strains of S. epidermidis that his group tested also produced PGA, as did six other genetically related Staphylococcus pathogens. "This could be important to vaccine development because the PGA is present in every strain of the organism," he added.
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 defence, 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.
The challenge of producing antibiotics to kill drug resistant bacteria will continue as bacteria will continue to find ways of becoming resistant to drugs. The main problem is the lack of new drugs in the pharmaceutical pipeline to keep pace with the evolution of drug-resistant bacteria, the so-called 'superbugs' It is an ongoing problem and will continue to pose a challenge in drug development.
The sheer indiscriminate nature of resistant bacterial strains has renewed the interest in structural targets that might prove effective against MRSA. Indeed, the annual cost for treating antibiotic resistant infections is approximately $30 billion (€25.7bn) in the USA alone.
The report of the study will appear in the March edition of The Journal of Clinical Investigation.
