Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era

Abstract

Antimicrobial peptides (AMPs) are an integral part of the innate immune defense mechanism of many organisms. Due to the alarming increase of resistance to antimicrobial therapeutics, a growing interest in alternative antimicrobial agents has led to the exploitation of AMPs, both synthetic and isolated from natural sources. Thus, many peptide-based drugs have been the focus of increasing attention by many researchers not only in identifying novel AMPs, but in defining mechanisms of antimicrobial peptide activity as well. Herein, we review the available strategies for the identification of AMPs in human body fluids and their mechanism(s) of action. In addition, an overview of the distribution of AMPs across different human body fluids is provided, as well as its relation with microorganisms and infectious conditions.

Keywords: antibacterial; antifungal; antiviral; human antimicrobial peptides; human biological fluids; peptidomics.

Figure 1

Phylogenetic tree representing all bacterial, viral, and fungal species targeted by human antimicrobial peptides found in body fluids. Created using phyloT.

Figure 2

Global network depicting the distribution of human antimicrobial peptides across biological fluids and their microbial targets. Rectangular nodes correspond to biofluids, circular nodes to target species, and each edge correspond to a given gene encoding one or more antimicrobial peptides. The thicker the edge, the stronger is the association of a biofluid to a pathogen, representing increased number of antimicrobial peptides defending against such pathogen in such biofluid. Also, pathogens represented by bigger nodes (e.g., Escherichia coli, Candida albicans, Staphylococcus aureus) represent those that are targeted by more antimicrobial peptides across different biofluids.

Figure 3

Distribution of species targeted by human antimicrobial peptides throughout human body fluids. Only most represented species are included.

Figure 4

Mechanisms of action of antimicrobial peptides. Antimicrobial peptides may either (1) cluster at the cell surface and cause membrane disruption by several different mechanisms (e.g., barrel staves, carpets, toroidal pores), (2) translocate into cells and impair intracellular organelle machineries, (3) impair protein–protein interactions, enzymatic cascades, and cytosolic signaling pathways, (4) interact with nucleic (not in the case of bacteria) acids, trap replication forks, and compromise nucleic acids as well as protein synthesis, (5) preclude several steps of viral replication, (6) inhibit genetic material trafficking, reverse transcriptase, and viral proteases, (7) block the interaction between virus and host cells (e.g., viral envelope glycoproteins gp120 and gp41 or co‐receptor CXCR4), compromising virus binding and entry, and (8) cause membrane lysis on enveloped viruses. See text for detailed description. Designed using Servier medical Art.