Antimicrobial peptides (AMPs) are the indispensable components of the innate immune system in various species including humans, animals, and plants. They constitute the first line of defence against foreign attacks. AMPs are constitutively expressed or induced by inflammation or injury and have been identified at most sites of the human body that are normally exposed to microbes, such as the skin, intestinal mucosa, oral mucosa, lung, eye, and reproductive tract.

One of the key advantages of AMPs over pharmaceutical antibiotics is the ability of some of these peptides to also modulate immune responses. In fact, in addition to their direct antimicrobial activity, AMPs can protect the host by a range of mechanisms: chemotactic activity, attracting leukocytes; modulation of host-cell responsiveness to TLR ligands; stimulation of angiogenesis; enhancement of leukocyte/monocyte activation; and differentiation and modulation of the expression of proinflammatory cytokines/chemokines. One indirect effect of the AMPs is their role in shaping the composition of the commensal microbiota, thereby contributing to the maintenance of skin and intestinal homeostasis. AMPs hold considerable promise for translational applications but developing their potential will require more sophisticated foundational understanding. These AMPs have been demonstrated to have their own advantages over the traditional antibiotics with a broad-spectrum of antimicrobial activities including anti-bacteria, anti-fungi, anti-viruses, and anti-cancers, and even in overcoming bacterial drug-resistance. The natural AMPs exist in a variety of organisms and are not stable, have a short half-life, can exert toxic side effects, and in particular may have severe hemolytic activity. Synergies between AMPs and conventional antibiotics should be exploited to rescue drugs that are currently lost due to resistance. The biochemical properties and pharmacodynamics of AMPs make them far more refractory to resistance evolution than conventional antibiotics. Translational use of AMPs in clinical and other applied settings will be greatly enhanced by understanding how specific AMPs function in their natural contexts and how their evolutionary history may predict their future utility. If we combine the insights from the evolutionary diversification of the AMPs, their activity in the context of synergistic cocktails, and our growing understanding of how to limit resistance evolution, we may avoid repeating the mistakes that have resulted in the current crisis of antibiotic resistance.

In this Special Issue, we encourage the authors to disseminate innovative studies on the involvement of antimicrobial peptides in host-pathogen interactions and to introduce interesting perspectives on their potential therapeutic use. Original research and review articles are welcome.

Potential topics include but are not limited to the following:

• Antimicrobial resistance
• Human microbiota
• Inflammation
• Host-pathogen interaction
• Innate immunity
• Translational medicine
• Homeostasis
• Properties and functions of antimicrobial peptides