Scientists are planning for a future in which superbugs gain the upper hand against our current arsenal of antibiotics. One emerging class of drug candidates, called AMLPs (antimicrobial lipopeptides), shows promise, and an article published in the August 18, 2015 issue of the Biophysical Journal explains why: they selectively kill bacterial cells, while sparing mammalian host cells, by clumping together into microscopic balls that stick to the bacterial membrane--a complex structure that will be slower to mutate and thus resist drugs. "The pressing need for novel antibiotics against resistant strains of bacteria and fungi has become a global medical concern," says senior study author Dr. Alan Grossfield of the University of Rochester Medical Center in New York. "Our new insights into how AMLPs work as groups, rather than individually, could optimize the development of these molecules as a new class of anti-resistance antibiotics." AMLPs could represent a promising alternative to traditional antibiotics. Past studies have shown that these synthetic compounds have potent activity against a range of pathogens and can clear infections in mice. Moreover, AMLPs are less vulnerable to evolved resistance because they disrupt the structure and function of microbial membranes. To evolve drug resistance, the microbes would require many big changes to alter the mixture of lipids composing the membrane. In addition, a variety of critical proteins embedded in the membrane depend on the membrane's current composition of lipids, so membrane changes that would prevent AMLP function would also tend to hinder the function of the bacteria's own membrane proteins. Despite their advantages, progress in developing AMLPs suitable for the clinic has been limited by the lack of a molecular-level understanding of their mode of action.
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