A study of how the immune system reacts to strains of antibiotic-resistant Staphylococcus aureus bacteria--emerging strains that sicken otherwise healthy people, or so-called "community-acquired" infections--has shown for the first time that these strains are more deadly and better at evading human immune defenses than more common S. aureus strains that originate in hospitals and other health-care settings.
In a paper released today online in The Journal of Immunology, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, describe how community-acquired S. aureus strains that survive treatment with the methicillin family of antibiotics can evade immune defenses. Infections from community-acquired methicillin-resistant S. aureus, or MRSA, are difficult to treat and are increasing nationally at an alarming rate, say experts.
Scientists at NIAID's Rocky Mountain Laboratories (RML) in Hamilton, MT, and colleagues examined the ability of MRSA strains to cause disease in mice and avoid destruction by human white blood cells called neutrophils. Neutrophils, which typically ingest and then kill harmful bacteria, make up about 60 percent of all white blood cells and are the first line of defense against bacteria. Scientists know that community-acquired strains differ from hospital strains, but they don't know why the community strains cause more serious infection in otherwise healthy people.
The work also identified specific S. aureus genes that potentially control the bacterium's escape from neutrophils. Among thousands of S. aureus genes analyzed in the five different strains used in the study, the scientists identified a large group of genes whose role in helping spread infection is unknown. RML's Frank DeLeo, Ph.D., the investigator who directed the study, and colleagues plan to determine if some of the unknown genes help promote disease. If they can learn which genes control the ability of S. aureus to evade and destroy neutrophils, their work could lead to new medical treatments.
"Each day physicians around the world are stymied by the inability to effectively treat patients suffering from severe S. aureus infections," says NIAID Director Anthony S. Fauci, M.D. "There is a critical need to develop new treatments against late-stage disease caused by antibiotic-resistant strains, and this promising work offers several 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 a community, it will make treatment of common infections much more difficult." The April 7, 2005, issue of The New England Journal of Medicine refers in an editorial to "… an epidemic of MRSA in the community."
S. aureus strains acquired in health-care settings can be challenging to resolve because of antibiotic resistance, which limits the choices for treatment. But the situation can become more serious with the newer community-acquired strains, says Dr. DeLeo. "We do not know why cases of community-acquired MRSA infections are increasing, let alone how they flourish," he says. But scientists do know the community strains can cause more severe forms of disease.
Mild S. aureus infections such as impetigo, which typically forms small blisters on the faces of children, or cellulitis, an inflammation of skin or muscle tissue, can easily be treated and usually resolve in a matter of days. But S. aureus disease also can be much more severe and difficult to treat, affecting vital organs and leading to toxins poisoning the blood and infection overwhelming the heart. One of the most severe types of disease is necrotizing pneumonia, where bacteria destroy lung tissue.
"The reason that some mild infections become severe or fatal is not well understood, but virulence is often associated with certain strains," says Jovanka Voyich, Ph.D., of RML, the study's lead author. To cause human disease, bacterial pathogens must avoid being killed by neutrophils. "These results," says Dr. Voyich, "suggest that community-acquired MRSA causes disease in healthy people in part because it has enhanced ability to circumvent killing by neutrophils."