A new study published in the September 11, 2009 issue of Science
by researchers at the NYU School of Medicine reveals a conceptually novel
mechanism that plays an important role in making human pathogens like Staphylococcus
aureus and Bacillus anthracis resistant to numerous antibiotics. The study led
by Evgeny A. Nudler, PhD, The Julie Wilson Anderson Professor of Biochemistry
at NYU Langone Medical
Center, provides evidence
that Nitric Oxide, or NO, is able to alleviate the oxidative stress in bacteria
caused by many antibiotics and also helps to neutralize many antibacterial
compounds. Eliminating this NO-mediated bacterial defense renders existing
antibiotics more potent at lower, less toxic, doses. With infectious diseases
the major cause of death worldwide, the study paves the way for new ways of
combating bacteria that have become antibiotic resistant.
NO is a small molecule composed of one atom of oxygen and
one of nitrogen. It was known as a toxic gas and air pollutant until 1987, when
it was first shown to play a physiological role in mammals, for which a Nobel
Prize was later awarded. NO has since been found to take part in an
extraordinary range of activities including learning and memory, blood pressure
regulation, penile erection, digestion and the fighting of infection and
cancer. A few years ago, the Nudler's group from NYU demonstrated that bacteria
mobilize NO to defend against the oxidative stress. The new study from the same
group supports the radical idea that many antibiotics cause the oxidative
stress in bacteria, often resulting in their death, whereas NO counters this
effect. This work suggests scientists could use commercially available
inhibitors of NO-synthase, an enzyme producing NO in bacteria and humans, to
make antibiotic resistant bacteria like MRSA and ANTHRAX more sensitive to
available drugs during acute infection.
"Developing new medications to fight antibiotic
resistant bacteria like MRSA is a huge hurdle, associated with great cost and
countless safety issues," says Nudler. "Here, we have a short cut,
where we don't have to invent new antibiotics. Instead, we can enhance the
activity of well established ones, making them more effective at lower doses."
"We are very excited about the potential impact of this
research in terms of continuing to push the boundaries of research in the area
of infectious diseases," said Vivian S. Lee, MD, PhD, MBA, vice dean for
science, senior vice president and chief scientific officer of NYU Langone
Medical Center. "With the emergence of drug resistant bacteria, it's
imperative that researchers strive to find conceptually new approaches to fight
these pathogens."
The study by Nudler and his colleagues was funded by a 2006
Pioneer Award from the National Institutes of Health in Bethesda, Maryland.
The Pioneer Award, a $2.5 million grant over five years, is designed to support
individual scientists of exceptional creativity who propose pioneering and
possibly transforming approaches to major challenges in biomedical and
behavioral research.
NYU Langone Medical Center
/ New York University School of Medicine
