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Scientists are working towards developing antibiotics that can accurately target infectious bacteria. Increased specificity could target antibiotic resistance and keep good bacteria from being attacked by broad-spectrum antibiotics.
The method is based on phage display, a proven strategy used to create and screen peptide libraries containing billions of different composite members displayed on bacteriophage. While a powerful tool, phage display has been limited to use with the peptides of natural amino acids.
Screening of this chemical enhanced library against live bacteria produced powerful, highly-selective probes to target two deadly antibiotic-resistant bacterial pathogens: methicillin-resistant Staphylococcus aureus and colistin-resistant Acinetobacter baumannii, the team reported in an article titled “Phage Display of Dynamic Covalent Binding Motifs Enables Facile Development of Targeted Antibiotics.”
The designer chemical warheads introduce into the phage library a “reversible covalent binding mechanism,” which is absent in peptides of natural amino acids. The chemically enhanced peptide library allows potent and selective targeting of a bacterium of interest, overcoming biological conditions that interfere with bonding to pathogens and avoiding healthy human cells.
The ‘warhead’ allows molecules with enhanced potency and selectivity toward a bacterial strain of interest. Attaching generic toxin to the bacterium-targeting molecules, a significant step forward imparting specificity in the treatment of the two strains of bacterium.
Modified phage library can be a powerful, multipurpose tool for generating imaging agents to confirm a suspected bacterial infection. These probes will go around and look for infected bacteria.
Attaching an antibiotic and the probe will serve to deliver the toxin to the only that strain of bacteria, this could be applicable to a wide range of bacterial pathogens, enabling the development of targeted antibiotics. Advances in targeted antibiotics will improve patient care, and reduce the “strain” placed on necessary bacteria and their evolution of antibiotic resistance.
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