It used to be that antibiotics could be trusted to rid the body of a host of bacterial diseases. Today, however, emerging strains of antibiotic-resistant bacteria are speeding ahead, threatening to make existing drugs obsolete. Now, researchers at the Weizmann Institute of Science have developed an original approach that may lead to a radically new way of treating bacterial infections. Natural detergent-like mechanism may lead to potent antimicrobial drugs
Insects, frogs and, as was recently discovered, humans, have a clever first line of defense against bacterial infections. This defense consists of peptides, or protein fragments, that zap the bacteria, literally spilling their "guts." Prof. Yechiel Shai of the Biological Chemistry Department and his team studied the way these peptides work and found that peptide strategy is as ingenious as it is simple: similar to a detergent or soap that dissolves fatty stains, peptides attach themselves to a bacterium and dissolve a portion of its membrane, which is made of a fatty substance. Once its membrane is punctured, the contents of the bacterium spill out and it dies on the spot.
Having characterized this bacteria-bashing mechanism, Shai's team went on to synthesize novel antimicrobial peptides that are more stable and long-lasting than the natural ones. They hope that these peptides will become the basis for potent antibacterial drugs. Because the new peptide materials kill bacteria instantly, it's unlikely that germs will get a chance to develop resistance against the medication.
Another major advantage of the new peptides is their simplicity. In contrast to antibiotics, which must perform the complicated task of penetrating bacteria and interfering with their functioning, the peptides simply attach themselves to bacterial membranes.
The Weizmann scientists have discovered that peptide attachment depends primarily on chemical composition, not structure. As a result, a synthetic peptide does not require a particularly good fit to be effective. This simplicity should make it relatively easy to produce such peptides in large quantities and to design a large family of these compounds geared to kill different types of bacteria.
Moreover, the peptides should not cause adverse reactions. As opposed to currently available antibiotics, which can destroy cells indiscriminately, the peptide materials have been engineered to kill only bacteria, not body cells. This selectivity is based on the fact that bacterial membranes are negatively charged. The peptides interact only with the negatively charged membranes but not with the neutral charge found on the surface of regular body cells.
The new materials have been shown to work in a test tube, and will soon be tested in laboratory animals. They are being developed for clinical use by a new start-up company, BALM Ltd., created by Pamot Venture Capital Fund and Yeda Research & Development Co. Ltd., the Weizmann Institute's technology transfer arm.
The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.