Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.

Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

Bacteriocins of gram-positive bacteria.

Antimicrobial peptides have been isolated and characterized from tissues and organisms representing virtually every kingdom and phylum, ranging from prokaryotes to humans. Yet, recurrent structural and functional themes in mechanisms of action and resistance are observed among peptides of widely diverse source and composition. Biochemical distinctions among the peptides themselves, target versus host cells, and the microenvironments in which these counterparts convene, likely provide for varying degrees of selective toxicity among diverse antimicrobial peptide types. Moreover, many antimicrobial peptides employ sophisticated and dynamic mechanisms of action to effect rapid and potent activities consistent with their likely roles in antimicrobial host defense. In balance, successful microbial pathogens have evolved multifaceted and effective countermeasures to avoid exposure to and subvert mechanisms of antimicrobial peptides. A clearer recognition of these opposing themes will significantly advance our understanding of how antimicrobial peptides function in defense against infection. Furthermore, this understanding may provide new models and strategies for developing novel antimicrobial agents, that may also augment immunity, restore potency or amplify the mechanisms of conventional antibiotics, and minimize antimicrobial resistance mechanisms among pathogens. From these perspectives, the intention of this review is to illustrate the contemporary structural and functional themes among mechanisms of antimicrobial peptide action and resistance.

Mechanisms of Antimicrobial Peptide Action and Resistance

Lactic acid bacteria produce a variety of bacteriocins that have recently come under detailed investigation. The biochemical and genetic characteristics of these antimicrobial proteins are reviewed and common elements are discussed between the different classes of bacteriocins produced by these Gram-positive bacteria.

Genetics of bacteriocins produced by lactic acid bacteria

Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides.

Dr. Alfred S. Ketcham was named Clinical Director of the National Cancer Institute. His ap­ pointment was announced by Dr. Carl G. Baker, NCI Director. Dr. Ketcham, who assumed his new duties Sept. 1, is a specialist in surgical treatment for cancer, with emphasis on disease of the head and neck area. He has developed a program of research on the problems of ex­ perimental and clinical metastasis, or spread, of cancer. He also directed research which demonstrated the ineffectiveness of the laser beam as a surgical tool in cancer therapy. Dr. Ketcham received his B.S. degree from Hobart College in 1945, and his M.D. degree from the University of Roch ester School of Medicine in 1949. His internship was served at the Na­ tional Naval Medical Center in Bethesda. He completed surgical training

The structure of nisin.

Mechanisms of action of corticotropin-releasing factor and other regulators of corticotropin release in rat pituitary cells.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2888%2980077-2

Synthetic magainin analogues with improved antimicrobial activity

Based on modifications to enhance the α-helical structure of the broad spectrum antibiotic magainin 2, a series of analogues have been synthesized which display an increase up to two orders of magnitude in antimicrobial activity and, in the most favorable case, no appreciable increase in hemolytic activity over magainin 1 at the concentrations tested.

John L. Morell

Papers

The structure of nisin.

Mechanisms of action of corticotropin-releasing factor and other regulators of corticotropin release in rat pituitary cells.

Synthetic magainin analogues with improved antimicrobial activity

Synthetic magainin analogues with improved antimicrobial activity

Properties and regulation of high-affinity pituitary receptors for corticotropin-releasing factor.