Non-membrane targets of antimicrobial peptides: novel therapeutic opportunities?

Abstract

AbstractThe emergence and rapid spread of multiresistant bacteria necessitates every effort to develop new classes of antibiotics with novel targets and modes of action. One potential source of novel antibiotics is the cationic antimicrobial peptides (AMPs), which constitute an important component of the innate immune system in a variety of organisms. Most AMPs exert their activity by interacting with bacterial membranes, thus perturbing their permeability. However, an increasing number of peptides are being described that translocate across the bacterial membranes and act on intracellular targets in bacteria. These non-membrane-active AMPs have been shown to bind and inactivate intracellular biopolymers such as nucleic acids and proteins without destroying or remaining attached to the bacterial membranes. As such, they have emerged as viable candidates for the treatment of human infections. In this chapter, we focus on the six well-characterized, non-membrane-active AMPs (buforin II, PR-39, indolicidin, apidaecin, drosocin and pyrrhocoricin) and discuss whether binding of these peptides to their intracellular targets correlates with bacterial cell death. The potential exploitation of these peptides as human therapeutics is also discussed.