Delivery of Antibiotics by Cell-Penetrating Peptides to Kill Intracellular Pathogens

In the last decades, the increasing rate of multidrug-resistant bacteria to classical antibiotics has driven research towards identification of other means to fight bacterial infections. In this context, intracellular and/or invasive facultative intracellular bacteria represent a particular problem as common antimicrobials are often not able to reach an effective intracellular concentration. In this regard, cell-penetrating peptides (CPP) can mediate the internalization of previously nonpermeable antimicrobial compounds into the cytoplasm of host cells where they efficiently kill intracellular pathogens. This chapter describes the conjugation of CPPs with antimicrobial agents for the delivery into infected cells. Furthermore, different antimicrobial activity assays will be described including the CPP-mediated delivery of an antimicrobial agent for the treatment of intracellular infections.