Staph germ undermines body's defenses

By RANDOLPH E. SCHMID, AP Science WriterSun Nov 11, 2:30 PM ET
The aggressive antibiotic-resistant staph infection responsible for thousands of recent illnesses undermines the body's defenses by causing germ-fighting cells to explode, researchers reported Sunday. Experts say the findings may help lead to better treatments.
An estimated 90,000 people in the United States fall ill each year from methicillin-resistant Staphylococcus aureus, or MRSA. It is not clear how many die from the infection; one estimate put it at more than 18,000, which would be slightly higher than U.S. deaths from AIDS.
The infection long has been associated with health care facilities, where it attacks people with reduced immune systems. But many recent cases involve an aggressive strain, community-associated MRSA, or CA-MRSA. It can cause severe infections and even death in otherwise healthy people outside of health care settings.
The CA-MRSA strain secretes a kind of peptide — a compound formed by amino acids — that causes immune cells called neutrophils to burst, eliminating a main defense against infection, according to researchers.
The findings, from a team of U.S. and German researchers led by Michael Otto of the National Institute of Allergy and Infectious Diseases, appeared in Sunday's online edition of the journal Nature Medicine.
While only 14 percent of serious MRSA infections are the community associated kind, they have drawn attention in recent months with a spate of reports in schools, including the death of a 17-year-old Virginia high school student.
Both hospital-associated and community-associated MRSA contained genes for the peptides. But their production was much higher in the CA-MRSA, the researchers said.
The compounds first cause inflammation, drawing the immune cells to the site of the infection, and then destroy those cells.
The research was conducted in mice and with human blood in laboratory tests.
Within five minutes of exposure to the peptides from CA-MRSA, human neutrophils showed flattening and signs of damage to their membrane, researchers said. After 60 minutes, many cells had disintegrated completely.
"This elegant work helps reveal the complex strategy that S. aureus has developed to evade our normal immune defenses," Dr. Anthony S. Fauci, NIAID director, said in a statement. "Understanding what makes the infections caused by these new strains so severe and developing new drugs to treat them are urgent public health priorities."
Dr. George G. Zhanel, a medical microbiologist at the University of Manitoba in Canada, said the study was the first he had seen that identifies the peptides involved.
This shows at least one of the reasons CA-MRSA is able to cause serious problems, Zhanel, who was not part of the research team, said in a telephone interview.
Findings like this may help lead to better treatments, such as ways to neutralize the peptides or to activate the immune system to defeat them, he added.
Dr. Lindsey N. Shaw of the division of cell biology, microbiology and molecular biology at the University of South Florida, also was enthusiastic about the research.
"Specifically identifying a factor which seemingly makes CA-MRSA more pathogenic than HA-MRSA is a real find," Shaw, who was not part of the research group, said via e-mail. The "molecules identified in the study are indeed novel."
Zhanel noted that while hospital-based MRSA seemed to concentrate on "sick old people," the community-based strain can break out in on sports teams, prisons, cruise ships and other places where people are not necessarily sick or have weakened immune systems.
In a worrisome development, he noted that the more aggressive strains have started appearing in hospitals.
Dr. Clarence B. Creech, an assistant professor of pediatric infectious disease at Vanderbilt University, said every time scientists find a new way that staph uses to make people sick, "we open up the field of developing new vaccine targets and new drug targets."
"This is one of the papers we can look to as we develop new vaccines and drugs," Creech, who was not part of the research team, said in a telephone interview.
The research was funded by the National Institutes of Health, the German Research Council and the German Ministry of Education and Research.
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On the Net:
Nature Medicine: http://www.nature.com/naturemedicine
NIH background on MSRA: http://tinyurl.com/2w4amj