Cell-penetrating peptides: Enhancing antimicrobial efficacy against intracellular pathogens

Cell-penetrating peptides (CPPs) are naturally occurring or synthetic peptide sequences that possess the inherent capability to penetrate various cell types and concurrently carry hydrophilic substances and nanomaterials, for which cellular absorption is typically restricted. Alongside this fundamental action of cell entry without damaging the membrane, certain CPPs exhibit multivalent antimicrobial properties. The method they utilize to penetrate cells continues to be an unresolved aspect of the mystery. Direct translocation and endocytosis have been proposed as the primary mechanisms for internalization; however, vesicle budding and collapse have also been mentioned.  CPPs exhibiting antimicrobial properties (CPAPs) represent a distinct group of bioactive peptides that emerge as potential solutions for combating challenging intracellular infections. This brief review intends to highlight and pinpoint in the scientific literature prior studies and references concerning the effects of CPPs that are active against intracellular infectious pathogens, and it explores the antibacterial, antiviral, and antiparasitic properties of several cell-penetrating antimicrobial peptides. To date, CPAPs show potential for druggability in the translational medical application of CPPs either individually or alongside chemotherapeutics. Furthermore, CPAPs might serve as an intriguing option for drug development and the management of intracellular infections.