Date: 11/11/2007 Aggressive staph germ found to secrete compound that
attacks immune cells
By RANDOLPH E. SCHMID
AP Science Writer
WASHINGTON (AP) _ 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.
