Emerging Staph Strains Found To Be Increasingly Deadly And Deceptive

In a paper released today online in The Journal of Immunology,scientists from the National Institute of Allergy and InfectiousDiseases (NIAID), part of the National Institutes of Health, describehow community-acquired S. aureus strains that survive treatment withthe methicillin family of antibiotics can evade immune defenses.Infections from community-acquired methicillin-resistant S. aureus, orMRSA, are difficult to treat and are increasing nationally at analarming rate, say experts.

Scientists at NIAID's Rocky Mountain Laboratories (RML) inHamilton, MT, and colleagues examined the ability of MRSA strains tocause disease in mice and avoid destruction by human white blood cellscalled neutrophils. Neutrophils, which typically ingest and then killharmful bacteria, make up about 60 percent of all white blood cells andare the first line of defense against bacteria. Scientists know thatcommunity-acquired strains differ from hospital strains, but they don'tknow why the community strains cause more serious infection inotherwise healthy people.

The work also identified specific S. aureus genes thatpotentially control the bacterium's escape from neutrophils. Amongthousands of S. aureus genes analyzed in the five different strainsused in the study, the scientists identified a large group of geneswhose role in helping spread infection is unknown. RML's Frank DeLeo,Ph.D., the investigator who directed the study, and colleagues plan todetermine if some of the unknown genes help promote disease. If theycan learn which genes control the ability of S. aureus to evade anddestroy neutrophils, their work could lead to new medical treatments.

"Each day physicians around the world are stymied by theinability to effectively treat patients suffering from severe S. aureusinfections," says NIAID Director Anthony S. Fauci, M.D. "There is acritical need to develop new treatments against late-stage diseasecaused by antibiotic-resistant strains, and this promising work offersseveral new approaches."

According to the Centers for Disease Control and Prevention,"recent reports of 'community-acquired' MRSA infections raise concern... If MRSA becomes the most common form of Staphylococcus aureus in acommunity, it will make treatment of common infections much moredifficult." The April 7, 2005, issue of The New England Journal ofMedicine refers in an editorial to "... an epidemic of MRSA in thecommunity."

S. aureus strains acquired in health-care settings can bechallenging to resolve because of antibiotic resistance, which limitsthe choices for treatment. But the situation can become more seriouswith the newer community-acquired strains, says Dr. DeLeo. "We do notknow why cases of community-acquired MRSA infections are increasing,let alone how they flourish," he says. But scientists do know thecommunity strains can cause more severe forms of disease.

Mild S. aureus infections such as impetigo, which typicallyforms small blisters on the faces of children, or cellulitis, aninflammation of skin or muscle tissue, can easily be treated andusually resolve in a matter of days. But S. aureus disease also can bemuch more severe and difficult to treat, affecting vital organs andleading to toxins poisoning the blood and infection overwhelming theheart. One of the most severe types of disease is necrotizingpneumonia, where bacteria destroy lung tissue.

"The reason that some mild infections become severe or fatal isnot well understood, but virulence is often associated with certainstrains," says Jovanka Voyich, Ph.D., of RML, the study's lead author.To cause human disease, bacterial pathogens must avoid being killed byneutrophils. "These results," says Dr. Voyich, "suggest thatcommunity-acquired MRSA causes disease in healthy people in partbecause it has enhanced ability to circumvent killing by neutrophils."

NIAID is a component of the National Institutes of Health, an agencyof the U.S. Department of Health and Human Services. NIAID supportsbasic and applied research to prevent, diagnose and treat infectiousdiseases such as HIV/AIDS and other sexually transmitted infections,influenza, tuberculosis, malaria and illness from potential agents ofbioterrorism. NIAID also supports research on transplantation andimmune-related illnesses, including autoimmune disorders, asthma andallergies.

Reference: J Voyich et al. Insights into mechanisms used byStaphylococcus aureus to avoid destruction by human neutrophils. TheJournal of Immunology 175(6):3907-19 (2005).

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