The complexities of antibiotic action

Mol Syst Biol. 3: 142Antibiotics are arguably the most successful medicine on the planet, but the one under huge threat from antibiotic resistance in the face of diminishing new antimicrobial discovery efforts (Hancock, 2007). One of the great hopes for discovering new antibiotics arose when whole‐genome sequencing came of age in 1995 with the decoding of the Haemophilus influenzae genome, followed rapidly by those of many other pathogens. Although this offered antibiotics researchers a window into every possible antibiotic target and stimulated massive efforts in Pharma and Biotech to uncover and exploit these targets, we have not seen a single new antibiotic arising from such studies. The reason is elusive, but could relate to the concept that antibiotics have much more complex mechanisms and targets than previously hypothesized (see Brazas and Hancock, 2005a for discussion). Indeed, a plethora of microarray studies have indicated that all studied antibiotics induce or repress dozens to hundreds of genes at or below their minimal inhibitory concentrations (MIC), and these patterns of expressed genes (signatures) appear to relate to the general mechanism of action of a particular antibiotic, with signatures for cell wall synthesis inhibition, …