News Release

Antimicrobial peptides: new weapons to fight infection

Peer-Reviewed Publication

Georgetown University Medical Center

In a review article published in the January 24 issue of the journal Nature, Michael Zasloff, MD, PhD, Georgetown University Medical Center’s Dean of Research and Translational Science, describes how antimicrobial peptides, molecules that exist throughout the plant and animal kingdoms, are inspiring the design of new antibiotics that may help conquer the growing problem of resistance to conventional antibiotics.

Defending the multicellular organism in which they live, antimicrobial peptides target a disease-carrying microbe’s bacterial membrane, which Dr. Zasloff labels “a previously under-appreciated microbial Achilles heel,” making it difficult for the microbe to resist their assault. Every plant and animal species harbors a unique, specific collection of antimicrobial peptides, Dr. Zasloff reports, tuned to defend the organism against microorganisms that it will encounter.

The study of antimicrobial peptides in plants and animals has provided insights into the innate defense systems that permit multicellular organisms, including humans, to live in harmony with microbes, Dr. Zasloff notes. Insects, octopuses and starfish, for example, rely heavily on antimicrobial peptides for defense against deadly microbes, and do so quite effectively without the help of lymphocytes, a thymus or antibodies.

“Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes,” writes Dr. Zasloff. “How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defense? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?”

Laboratory and clinical studies “confirm emergence of resistance against antimicrobial peptides is less probable than observed for conventional antibiotics,” according to Dr. Zasloff. This, he believes, provides ample impetus to develop both natural and man-made antimicrobial peptides into therapeutically useful agents for the treatment and prevention of many infectious diseases.

Over the past 15 years, Dr. Zasloff’s own scientific research has focused on the innate immune systems of animals. While working at the NIH, he discovered that frogs produced powerful antibiotics in their skin, which he named “magainins,” from the Hebrew word for “shield.” When magainin comes into contact with certain cell membranes, including those of many disease causing microbes, it assumes a helical coil shape and breaks through the membrane into the cell, destroying it. Dr. Zasloff and his research team also were the discoverers of squalamine in sharks. Squalamine was the first of a novel class of steroids which has shown to be effective against solid tumors. It is currently in Phase II clinical trials being evaluated for treatment of non-small cell lung cancer and refractory ovarian cancer.

“The innate antibiotics of animals were discovered by scientists who were bewildered by the many examples in nature of plants and animals living in apparent harmony with microbes,” said Dr. Zasloff. “During this era of computer-based education and research, we should not forget that direct observation of the natural world still remains an important source of insight and discovery.”

Earlier this month Dr. Zasloff was named Georgetown University Medical Center’s first Dean of Research and Translational Science to oversee biomedical research and its translation from the laboratory to patient care.

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Georgetown University Medical Center includes the nationally ranked School of Medicine, School of Nursing and Health Studies, the Lombardi Cancer Center and a biomedical research enterprise.


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