Antibiotic-resistant
bacteria continue to be a global concern with devastating repercussions, such
as increased healthcare costs, potential spread of infections across
continents, and prolonged illness.
However, researchers at Brigham and Women's Hospital
(BWH) could change the playing field of man versus bacteria. Charles Serhan,
PhD, director of the BWH Experimental Therapeutics and Reperfusion Injury
Center, has identified pathways of naturally occurring molecules in our bodies
that can enhance antibiotic performance.
The study will be electronically published on April
25, 2012 in Nature.
Mice infected with Escherichia coli (E. coli) or
Staphylococcus aureus (S. aureus) bacteria were given molecules called
specialized pro-resolving mediators (SPMs) along with antibiotics. SPMs are
naturally found in our bodies, and are responsible for mediating
anti-inflammatory responses and resolve inflammation. An anti-inflammatory
response is the body's attempt to protect itself from infectious agents and
initiate the healing process.
The researchers found that specific types of SPM
molecules, called resolvins and protectins, were key in the anti-inflammatory
response to limit tissue damage by stimulating the body's white blood cells to
contain, kill and clear the bacteria.
Administered with antibiotics, resolvins and
protectins heightened immune response by commanding white blood cells to attack
and engulf the bacteria, thereby quickly reducing the amount of bacteria in the
blood and tissues.
RvD5-a type of resolvin-in particular was also
helpful in regulating fever caused by E.coli, as well as counter-regulating
genes responsible for mounting excess inflammation associated with infections;
hence, limiting the collateral damage to the body while fighting infection.
Serhan and colleagues are the first to demonstrate
RvD5, as well as its actions against bacterial invasion. The BWH team,
collaborating with Fredrik Bäckhed, PhD of the Sahlgrenska Center for
Cardiovascular and Metabolic Research in Sweden, found that germ-free animals
produce high levels of resolvins.
When Nan Chiang, PhD, BWH Experimental Therapeutics
and Reperfusion Injury Center, and lead study author, added these natural
mediators together with antibiotics, less antibiotics were needed. This
demonstrated for the first time that stimulating resolution programs can limit
negative consequences of infection.
"How the body responds to inflammation has been
the subject of Dr. Serhan's work for more than 20 years, and his new study is
important for understanding that sequence of events," said Richard Okita,
PhD, National Institute of General Medical Sciences, National Institutes of
Health which funded the research. "One of the particularly exciting
findings is that SPMs can enhance the effectiveness of antibiotics, potentially
lowering the amount needed to treat infections and reducing the risk of
bacteria developing resistance."
According to the researchers, another advantage of
SPMs is that, unlike anti-inflammatory drugs (e.g. aspirin, steroids,
ibuprofen), SPMs do not cripple the body's normal immune response.
"Anti-inflammatory agents are widely known to
be immunosuppressive," said Serhan. "Now we have naturally occurring
molecular pathways in our bodies that work like these agents and stimulate
bacterial containment and resolution of infections, but do not come with the
side effect of being immunosuppressive."
E. coli infections continue to be both a world- and
nationwide concern. In the United States, E. coli infections account for
approximately 270,000 cases per year. S. aureus is responsible for causing skin
infections and a majority of hospital-acquired infections.
This research was 100 percent supported by the
following grants from the National Institutes of Health and National Institute
of General Medical Sciences: P01GM095467 and R01GM38765 (CNS).
Source: Brigham and Women's Hospital
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