Targeting Bacterial Gas Defenses Allow for Increased Efficacy of Numerous Antibiotics

Researchers discover role of H2S as defense mechanism against oxidative stress and antibiotics


Although scientists have known for centuries that many bacteria produce hydrogen sulfide (H2S) it was thought to be simply a toxic by-product of cellular activity. Now, researchers at NYU School of Medicine have discovered H2S in fact plays a major role in protecting bacteria from the effects of numerous different antibiotics.

In the study led by Evgeny Nudler, PhD, the Julie Wilson Anderson Professor of Biochemistry at NYU School of Medicine, researchers found evidence that H2S acts as a general defense mechanism against oxidative stress, the process through which many antibiotics kill bacteria. This information provides the basis for developing new techniques to suppress this universal bacterial defense mechanism and make bacteria more susceptible to antibiotics at lower doses. It also paves the way for reversing antibiotic resistance in human pathogens such as Staphylococcus, Pseudomonas, E. coli, and many others. The study's findings were published online on November 17 edition of Science.

"Surprisingly little has been known about H2S biochemistry and physiology in common bacteria" said Dr. Nudler. "We are excited about the potential impact this research may have on the growing problem of microbial resistance. These findings suggest a conceptually new approach, an adjuvant therapy that targets bacterial gas defenses and thus increases the efficacy of many clinically used antibiotics."

More specifically, the study showed that integrated mechanism of H2S-mediated protection against oxidative stress also protects against antibiotics. The research provides direct support for the emerging concept of the pro-oxidative action of many antibiotics. In addition, the study demonstrates that bacteria that generate both H2S and nitric oxide (NO) simultaneously, such as B. anthracis (a causative of anthrax), cannot survive without both gases, even under normal growth conditions. One gas makes up for the lack of the other and at least one of them is essential.

In a previous study Dr. Nudler and his colleagues demonstrated that NO plays a similar role in protecting bacteria from antibiotics (Science September 9, 2009). However, because NO is present in only a limited number of bacteria while hydrogen sulfide synthesis occurs in essentially all bacteria, the practical implications of this new finding is extremely wide-ranging.


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About NYU School of Medicine

NYU School of Medicine, the medical school of NYU Medical is one of the nation's preeminent academic institutions dedicated to achieving world class medical educational excellence. For 170 years, NYU School of Medicine has trained thousands of physicians and scientists who have helped to shape the course of medical history and enrich the lives of countless people. An integral part of NYU Langone Medical Center, the School of Medicine at its core is committed to improving the human condition through medical education, scientific research and direct patient care. The School also maintains academic affiliations with area hospitals, including Bellevue Hospital, one of the nation's finest municipal hospitals where its students, residents and faculty provide the clinical and emergency care to New York City's diverse population, which enhances the scope and quality of their medical education and training. Additional information about the NYU School of Medicine is available at http://school.med.nyu.edu/.

Contact: Christopher Rucas
NYU Langone Medical Center / New York University School of Medicine
Christopher.Rucas@nyumc.org
212-404-3525
 

Posted: November 2011

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