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Fighting antibiotic resistance with 'molecular drill bits'

s from many sources, including fly larvae, frog skin and mammalian immune system cells. The molecules come in different shapes, lengths and with other varying traits. But one thing they all have in common is that they somehow break through bacterial cell walls, the tough outer layers that provide structural support and protection. When Belfort found out about AMPs' mode of action, he aptly dubbed them "molecular drill bits."

Intrigued by their potential, Belfort scoured recent work on the peptides and discovered a database filtering technique developed by another group, reported in 2012. It's a kind of design-your-own-AMP model.

Using the database filtering technology, Belfort's lab designed and synthesized three novel AMPs designed to drill into the thick walls of tuberculosis cells. When they tested them in the lab against Mycobacterium tuberculosis and another similar bacteria, all three AMPs killed the bacteria. One worked better than the others but not as well as kanamycin, which is one of several antibiotics in the arsenal against TB that some strains have developed resistance against.

Belfort's team is now focused on improving their designs and understanding exactly how AMPs work. The group is also developing a laboratory test that will allow them to tell within hours rather than weeks if an AMP is working against Mycobacterium tuberculosis.

If developed into pharmaceuticals, AMPs could have the additional benefit of overcoming the very challenge they're designed to meet: drug-resistance. AMPs attack bacteria's walls, or cell membranes, which have been conserved through a long history of evolution.

"It's going to be much more difficult for a bacterium that's been around for millions of years to reconfigure its membrane," Belfort said. "That's the core protective structure that has helped it survive this long."

Contact: Michael Bernstein
214-853-8005 (Dallas Press Center, March 14-19)

Contact: Katie Cottingham, Ph.D.
214-853-8005 (Dallas Press Center, March 14-19)

American Chemical Society


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