Synthetic Antibacterial Molecule Kills Drug-Resistant Bacteria

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Many previously treatable bacterial diseases have re-emerged with a vengeance, largely immune to penicillin and its close relatives. Drug-resistant bacteria are now a global health threat. In its June 2000 report entitled "Overcoming Antimicrobial Resistance," the World Health Organization stated that the growing resistance of major infectious organisms has reduced the healing power of "once life-saving medications" to that of a "sugar pill." The report highlighted several serious consequences, including an estimated 14,000 deaths in the United States each year from hospital-acquired, drug-resistant infections. As bacteria continue to evade existing therapies, scientists race to stay ahead by developing new antibiotic drugs.

Dr. Samuel Gellman and coworkers at the University of Wisconsin, Madison have created a synthetic antibiotic molecule out of non-natural forms of amino acids called beta-amino acids. This "beta-peptide" mimics a class of natural antimicrobial molecules called magainins. These molecules exist in a wide variety of forms in nature and defend biological borders, such as skin, from invading bacteria. The beta-peptide has shown its antibiotic properties in the lab, killing both normal and drug-resistant strains of infectious bacteria, including a strain resistant to vancomycin--the "last resort" antibiotic that must be administered by IV in a hospital.

The beta-peptide has two promising characteristics that distinguish it from traditional antibiotics. In combination, these two factors could be enough to prevent bacteria from developing resistance. First, researchers believe that bacteria may have trouble developing resistance to the beta-peptide because bacterial defenses may not recognize its non-natural amino acids. Second, the magainins that the beta-peptide mimics have been around for millions of years, yet bacteria have not become resistant to them. The beta-peptide must undergo further testing in the form of animal and clinical studies before its usefulness as a drug is known. But even if the beta-peptide never becomes a drug, this work is remarkable because it began as an effort to look at the folding properties of molecules, not to create an antibiotic. The research shows that it is possible to design from scratch the structure of a protein with a desired biological action.


Porter EA, Wang X, Lee HS, Weisblum B, and Gellman SH. Non-haemolytic beta-amino-acid oligomers. Nature 2000;404:565.

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