Intracellular Targets of Antibacterial Peptides

The recent past witnessed a decrease in the number of new antibacterial compounds approved by the regulatory agencies and an almost complete lack of molecules killing bacteria by novel mechanisms of action. The broad spectrum antimicrobial agents currently on the market carry the potential, and indeed victims, of resistance developed against them. The need for new types of antimicrobial drugs coincides with the desire of developing lead molecules that act selectively on a single strain, or perhaps on a few closely related strains. Such selectivity would exclude the likelihood of the emergence of broad-range resistance. Intracellular bacterial targets, most prevalently proteins needed for the life cycle of bacteria, carry the potential to be a resourceful target for a new family of antimicrobial compounds. Inhibition of proteinaceous functions requires stereospecificity, and a drug structurally similar to the target proteins themselves. Indeed, some antibacterial peptides show selective inhibition of intracellular targets. A few native peptides and their designed analogs appear to kill only a limited number of bacterial strains. Identification of the binding sites on the target proteins would allow the design of strain-specific antibacterial and antifungal peptides without the fear of development of common resistance to these agents.