Does the cell wall of bacteria remain a viable source of targets for novel antibiotics?

Whether the bacterial cell wall remains a viable source of novel antibacterials is addressed here by reviewing screen and design strategies for discovery of antibacterials with a focus on their output. Inhibitors for which antibacterial activity has been shown to be due to specific inhibition of a reaction (antibacterially validated inhibitors) are known for 8 of the 14 conserved essential steps of the pathway. Antibacterially validated enzyme inhibitors exist for six of these steps. The possible obstacles to finding validated inhibitors of the remaining enzymes are discussed and some strategies are suggested. (c) 2005 Elsevier Inc. All rights reserved.