SNAPPy solution for fighting drug-resistant bacteria

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Science Translational Medicine  12 Oct 2016:
Vol. 8, Issue 360, pp. 360ec164
DOI: 10.1126/scitranslmed.aai9161

The discovery and use of antibiotics has changed the face of human medicine by dramatically reducing the severity and deadliness of infectious diseases. Unfortunately, the long-term use and misuse of these pharmaceuticals has created selective pressure on their targeted organisms, resulting in widespread drug resistance. Over 100 antibiotics were discovered from the 1920s through the 1980s, but very few new small molecule compounds have been identified over the past 30 years, indicating the need for a new approach. One such alternative approach has been antimicrobial peptides, which are components of the innate immune response that selectively kill bacterial cells. Although they are effective, antimicrobial peptides are expensive to manufacture and often have limited-spectrum effects. Recently, Lam et al. have demonstrated a method of fabricating new antimicrobial peptide-inspired nanomaterials with potent antimicrobial activity against a wide variety of drug-resistant Gram-negative bacteria.

Antimicrobial peptides usually act by creating small pores that can disrupt membrane integrity. While potent, each antimicrobial peptide often uses a single, very specific pore-forming action, which bacteria can avoid by changing their membrane structure. Lam et al. postulated that if they formulated nanoparticles with random cationic peptides grown off of a synthetic polymer core template, they may be able to generate a technology capable of carrying out broad-spectrum antimicrobial activity. These newly designed nanomaterials, termed structurally nanoengineered antimicrobial peptide polymers (SNAPPs), were found to have broad-spectrum antimicrobial behavior and disrupt the cell membranes and bioactivity of many different genera of known antibiotic-resistant Gram-negative bacteria. Interestingly, when the authors attempted to facilitate SNAPP antimicrobial resistance by giving sub-effective doses over 600 generations of bacterial growth, the lethal dose remained constant, indicating that resistance is not easily acquired. When SNAPPs were given to mice fighting an aggressive opportunistic infection (A. baumannii), they greatly decreased bacterial loads and improved neutrophil recruitment for bacterial strains with and without antimicrobial resistance.

The authors theorized that the antimicrobial behavior of SNAPPs results from their ability to make more complex and larger membrane pores, causing fragmentation or perforation, which is more difficult for the cells to acquire resistance to. Although further studies are needed to clarify the mechanism of action responsible for SNAPP bioactivity, Lam et al. provide considerable evidence for SNAPPs to serve as a broad-spectrum alternative to classical small molecule antibiotics and conventional antimicrobial peptides.

S. J. Lam et al., Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nat. Microbiol. 10.1038/nmicrobiol.2016.162 (2016). [Abstract]

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