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.

How are the expression patterns of gut antimicrobial peptides modulated by human gastrointestinal diseases? A bridge between infectious, inflammatory, and malignant diseases

“…Finally, it should be noted that reductions in the levels of constitutively expressed β‐defensins should not be always regarded as a bad indicator. For instance, and as recently reviewed, HBD‐1 is active not only against pathogenic bacteria but also against Gram‐positive commensal Bifidobacterium and Lactobacillus (which may in turn have protective effects by, for instance, decreasing tissue inflammation in the gut).…”

“…Nevertheless, these are not mutually restricted as 1 AMP may have multiple effects. As recently described, AMPs are classically known to cluster at the negatively charged membrane surface, thereby causing its disruption by forming different structures (barrel staves, carpets, or toroidal pores). Alternatively (or subsequently), AMPs can translocate into cells and impair intracellular organelle machineries, modulate protein‐protein interactions, enzymatic cascades, or cytosolic signalling pathways.…”

“…While each antimicrobial peptide (AMP) can display multiple functions, this family of defense molecules carries out the additional function of controlling bacteria abundance and composition. Both the lumen and the intestinal barrier membrane contain a diverse plethora of AMPs, which nonetheless share common properties contributing for their membranolytic or otherwise antimicrobial activity, namely, positive charges, hydrophobicity, and amphiphilicity …”

Targeting virulence factors as an antimicrobial approach: Pigment inhibitors

“…In addition, the utilization of bacterial viruses (phages) and predatory bacteria against pathogens is consistently a hot topic, not only due to a range of intrinsic differences in their mechanisms of action but also because of the virtually infinite diversity, although these strategies still have potential risks and problems such as dosing levels and schedules . Moreover, due to the high cost, unknown toxicity, and technical barriers associated with antimicrobial biotherapy, these therapies are still largely replaced with cheaper and safer broad‐spectrum antibiotics . Hence, chemotherapy that depends on artificial small molecules and natural products still dominates the current stage.…”

Drug delivery systems designed to overcome antimicrobial resistance

“…Over the last few decades, AMPs have garnered increasing interest, not only as potential ATB agents, but also as ATB carriers . AMPs, also called host defense peptides (HDPs), are small polycationic amphipathic peptides (often, with fewer than 50 amino acid‐sequences) that have been found in all multicellular organisms . In structural analysis, AMPs possess different secondary structures, often stabilized by disulfide bridges .…”