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Many factors contribute to bacterial membrane stabilization, including steric effects between lipids, membrane spontaneous curvature, and the difference in the number of neighboring molecules. This forum provides an overview of the physicochemical properties associated with membrane curvature and how this parameter can be tuned to design more effective antimicrobial peptides., Competing Interests: Declaration of interests C.F-N. provides consulting services to Invaio Sciences and is a member of the Scientific Advisory Boards of Nowture S.L., Peptidus, and Phare Bio. C.F-N. is also on the Advisory Board of the Peptide Drug Hunting Consortium (PDHC). The de la Fuente Lab has received research funding or in-kind donations from United Therapeutics, Strata Manufacturing PJSC, and Procter & Gamble, none of which were used in support of this work. C.F-N. is on the Advisory Board of Cell Reports Physical Science., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Antimicrobial peptides (AMPs) are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Their wide range of activity against pathogens, including Gram-positive and -negative bacteria, yeasts, fungi, and enveloped viruses makes them a fundamental component of innate immunity. Marra et al. (A. Marra, M. A. Hanson, S. Kondo, B. Erkosar, B. Lemaitre, mBio 12:e0082421, 2021, https://doi.org/10.1128/mBio.00824-21) use the analytical potential of Drosophila to show that AMPs and lysozymes play a direct role in controlling the composition and abundance of the beneficial gut microbiome. By comparing mutant and wild-type flies, they demonstrated that the specific loss of AMPs and lysozyme production results in changes in microbiome abundance and composition. Furthermore, they established that AMPs and lysozyme are particularly essential in aging flies. Studies of early emerging metazoans, other invertebrates, and humans support the view of an ancestral function of AMPs in controlling microbial colonization.

The gastrointestinal (GI) tract is equipped with robust immune defenses which protect the organism from infection. Enteric nerves are front and center in this defensive network, even in the most primitive organisms. Neuropeptides exhibit potent antimicrobial activity in the vicinity of the nerve and attract the innate and adaptive immune systems to help confine the invading agent. Alpha-synuclein (αS) has many biophysical characteristics of antimicrobial peptides and binds small vesicles such as those carrying endocytosed viruses. It is induced in nerve cells in response to viral and bacterial infections. It renders the nerve cell resistant to viral infection and propagation. It signals the immune system by attracting neutrophils and macrophages, and by activating dendritic cells. Most remarkably αS is trafficked to the central nervous system (CNS) conferring immunity in advance of an infection. Chronic GI infection or breakdown of the epithelial barrier can cause αS to accumulate and form neurotoxic aggregates. Overproduction of αS in the enteric nervous system (ENS) and its chronic trafficking to the CNS may damage nerves and lead to Parkinson's disease. Targeting the formation of αS aggregates in the ENS may therefore slow the progression of the disease. [ABSTRACT FROM AUTHOR]

Repair of tissue wounds is a fundamental process to re-establish tissue integrity and regular function. Importantly, infection is a major factor that hinders wound healing. Multicellular organisms have evolved an arsenal of host-defense molecules, including antimicrobial peptides ( AMPs), aimed at controlling microbial proliferation and at modulating the host's immune response to a variety of biological or physical insults. In this brief review, we provide the evidence for a role of AMPs as endogenous mediators of wound healing and their promising therapeutic potential for the treatment of non-life-threatening skin and other epithelial injuries. [ABSTRACT FROM AUTHOR]

Examines the widespread distribution of antimicrobial peptides among multicellular plants and animals. Diversity of peptides; Clusters of cationic and hydrophobic amino acids in distinct domains; Membrane target and basis of specificity.

Antimicrobial peptides (AMPs) provide broad spectrum antimicrobial defense in both healthy and injured skin. At high concentrations AMPs can damage normal human cells, resulting in necrosis or apoptotic death. In this issue Chammoro et al. (2009) describe a novel mechanism involving prostaglandin PGE2 that appears to explain how the keratinocyte, which secretes AMPs, can remain immune to self-inflicted AMP-induced apoptosis.Journal of Investigative Dermatology (2009) 129, 824–826. doi:10.1038/jid.2008.455 [ABSTRACT FROM AUTHOR]

The article presents research to understand antimicrobial peptides' natural biology and evolution in order to lessen the risk of collateral harm and avoid the resistance crisis facing conventional antibiotics. It discusses the pharmacodynamics and mechanisms of killing of antimicrobial peptides. It mentions the growing understanding of how to limit resistance evolution.

Discusses the role of trypsin in the processing of the Paneth cell defensin. Proteolytic maturation of the human Paneth cell antimicrobial peptide human α-defensin-5 (HD5); Storage of HD5 as a propeptide.

Presents information on antimicrobial peptides as a mechanism of defense against microbes. Discussion on the therapeutic properties of peptides; Mechanism of action of peptides; Reconstruction of antimicrobial peptides out of beta-amino acids.

A response by Michael Zasloff to a letter to the editor by Klaus Fellermann and colleagues to an article by P.Y. Ong and colleagues about endogenous antimicrobial peptides and skin infections in atopic dermatitis, which appeared in the October 10, 2003 issue, is presented.

Editorial. Discusses the role of antimicrobial peptides in health and disease. Defense chemicals of the epithelium; What has been learned from the immunity of insects; Functions of defensins and cathelicidins; Importance of the protective shield antimicrobial peptides provide.