Antibiotics for Emerging Pathogens

Toward New Scaffolds Most existing antibiotics are derived from a small number of core molecular structures or scaffolds. As more and more pathogens emerge that are resistant to existing antibiotics, Fischbach and Walsh (p. 1089) review why renewed efforts must be made to find not only new antibiotics but new scaffolds. Approaches in the areas of natural products, synthesis, and target-based discovery are all yielding promising antibiotics candidates. The battle against resistance should also involve researching narrow-spectrum antibiotics and using combination therapies to extend the usefulness of drugs with high intrinsic resistance rates. Antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent in hospitals and the community. New antibiotics are needed to combat these bacterial pathogens, but progress in developing them has been slow. Historically, most antibiotics have come from a small set of molecular scaffolds whose functional lifetimes have been extended by generations of synthetic tailoring. The emergence of multidrug resistance among the latest generation of pathogens suggests that the discovery of new scaffolds should be a priority. Promising approaches to scaffold discovery are emerging; they include mining underexplored microbial niches for natural products, designing screens that avoid rediscovering old scaffolds, and repurposing libraries of synthetic molecules for use as antibiotics.