Antibiotics for emerging pathogens

Abstract

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.

Fig. 1

Multidrug-resistant strains of these bacterial pathogens are on the rise.

Fig. 2

Synthetic tailoring is widely used to create successive generations of antibiotic classes. Scaffolds are colored black; peripheral chemical modifications are colored red. The quinolone scaffold is synthetic, while the other scaffolds are natural products.

Fig. 3

Between 1962 and 2000, no major classes of antibiotics were introduced.

Fig. 4

The chemical structures of new and underexplored antibiotic scaffolds mentioned throughout the text are organized by type into three categories: synthetic, semisynthetic, and natural product. For synthetic and semisynthetic scaffolds, core scaffolds are shown in black and variable positions are shown in red.

Fig. 5