Antimicrobial peptides with cell-penetrating activity as prophylactic and treatment drugs

Abstract

Health is fundamental for the development of individuals and evolution of species. In that sense, for human societies is relevant to understand how the human body has developed molecular strategies to maintain health. In the present review, we summarize diverse evidence that support the role of peptides in this endeavor. Of particular interest to the present review are antimicrobial peptides (AMP) and cell-penetrating peptides (CPP). Different experimental evidence indicates that AMP/CPP are able to regulate autophagy, which in turn regulates the immune system response. AMP also assists in the establishment of the microbiota, which in turn is critical for different behavioral and health aspects of humans. Thus, AMP and CPP are multifunctional peptides that regulate two aspects of our bodies that are fundamental to our health: autophagy and microbiota. While it is now clear the multifunctional nature of these peptides, we are still in the early stages of the development of computational strategies aimed to assist experimentalists in identifying selective multifunctional AMP/CPP to control nonhealthy conditions. For instance, both AMP and CPP are computationally characterized as amphipatic and cationic, yet none of these features are relevant to differentiate these peptides from non-AMP or non-CPP. The present review aims to highlight current knowledge that may facilitate the development of AMP's design tools for preventing or treating illness.

Keywords: antimicrobial peptides; autophagy; cell penetrating peptide; machine learning; microbiome.

Figure 1. The relevance of multifunctional AMP for health

AMP are amphipathic and cationic endowing interaction with anionic bacterial membranes, creating pores, and directly causing cell lysis. Furthermore, AMP with CPP activities also interact with cellular components such as DNA and ATP, which possess negatively charged groups, causing a disruption of their metabolism in bacteria. In some cell types like immune cells, AMP interact with receptors and/or induce autophagy, the release of cytokines and chemokines (with intrinsic antimicrobial activity), hence, promoting a feedback loop for autophagy resulting in the encapsulation and killing of bacteria (xenophagy). By considering these multiple functions of AMP with CPP activity, it may be possible to learn how the human body controls microbiota and autophagy to improve the health of the human population. Image created using ChemDraw.