A New Approach for Developing Antimocrobials

The world needs better methods of attacking resistant microbes. This is particularly true in the area of engineered bio-weapons. A new approach to antimocribial development at MIT appears to offer many possibilities for both treatment of routine resistant organisms, and treatment for anthrax and other potential bioweapons.

"In the last 40 years, there have been only two new classes of antibiotic drugs discovered and brought to the market," said graduate student Christopher Loose, lead author of a paper on the work that appears in the Oct. 19 issue of Nature. "There is an incredible need to come up with new medicines."

Loose, research associate Kyle Jensen and Professor Gregory Stephanopoulos of the Department of Chemical Engineering are focusing their attention on antimicrobial peptides, or short strings of amino acids. Such peptides are naturally found in multicellular organisms, where they play a role in defense against infectious bacteria.

The researchers' newly designed peptides were shown to be effective against dangerous microbes such as Bacillus anthracis (anthrax) and Staphyloccus aureus, a bacteria that spreads in hospitals and is frequently drug-resistant. The peptides may also be less likely to induce drug resistance in these bacteria, according to the researchers.

Antimicrobial peptides act by attaching to bacterial membranes and punching holes in them, an attack that is general to many different types of bacteria and is difficult for them to defend against. "There's no quick easy mutation fix for a bacteria to get around this non-specific membrane attack," said Loose.
....To design their new peptides, the researchers first came up with all possible 20-amino acid sequences in which each overlapping string of 10 amino acids conformed to one of the grammars. They then removed any peptides that had six or more amino acids in a row in common with naturally occurring peptides. Then, they threw out sequences that were very similar to each other and chose 42 peptides to test.

About half of the peptides displayed significant antimicrobial activity against two common strains of bacteria -- Escherichia coli and Bacillus cereus. That is a much higher success rate than one would expect from testing randomly generated sequences, and much higher than the success rate for peptides with the same amino acids as the designed sequences, but in a shuffled order.

"We've been able to focus our shotgun approach so that half of the time, we get a hit," said Loose.

In further tests, two of the designed peptides showed very high effectiveness against two types of especially dangerous bacteria, S. aureus and anthrax.

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There are other approaches to treating resistant bacteria that have similar promise. I am very hopeful that biotechnology will offer many solutions to the problems that conventional pharmacology has created.