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?

The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes Thus, despite the fact that all fish groups have functional kidneys, the gill epithelium is the site of many processes that are mediated by renal epithelia in terrestrial vertebrates Indeed, many of the pathways that mediate these processes in mammalian renal epithelial are expressed in the gill, and many of the extrinsic and intrinsic modulators of these processes are also found in fish endocrine tissues and the gill itself The basic patterns of gill physiology were outlined over a half century ago, but modern immunological and molecular techniques are bringing new insights into this complicated system Nevertheless, substantial questions about the evolution of these mechanisms and control remain

https://people.clas.ufl.edu/devans/files/PRVGill.pdf

The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste

Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.

Peptide Antimicrobial Agents

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake

Water-membrane soluble protein and peptide toxins are used in the defense and offense systems of all organisms, including plants and humans. A major group includes antimicrobial peptides, which serve as a nonspecific defense system that complements the highly specific cell-mediated immune response. The increasing resistance of bacteria to conventional antibiotics stimulated the isolation and characterization of many antimicrobial peptides for potential use as new target antibiotics. The finding of thousands of antimicrobial peptides with variable lengths and sequences, all of which are active at similar concentrations, suggests a general mechanism for killing bacteria rather than a specific mechanism that requires preferred active structures. Such a mechanism is in agreement with the “carpet model” that does not require any specific structure or sequence. It seems that when there is an appropriate balance between hydrophobicity and a net positive charge the peptides are active on bacteria. However, selective activity depends also on other parameters, such as the volume of the molecule, its structure, and its oligomeric state in solution and membranes. Further, although many studies support that bacterial membrane damage is a lethal event for bacteria, other studies point to a multihit mechanism in which the peptide binds to several targets in the cytoplasmic region of the bacteria.

Mode of action of membrane active antimicrobial peptides.

Characterization and distribution of neuropeptide Y in the brain of a caecilian amphibian.

Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: Potent activity against oral pathogens

Molecular Evolution of Somatostatin Genes

Receptor binding profile of neuropeptide γ and its fragments: Comparison with the nonmammalian peptides carassin and ranakinin at three mammalian tachykinin receptors

Neurotensin (NT) was isolated in pure form from the small intestine of the European green frog, Rana ridibunda, and its primary structure was established as pGlu-Ala-His-Ile-Ser-Lys-Ala-Arg-Arg-Pro-Tyr-Ile-Leu. This sequence contains five amino acid substitutions (Leu2→Ala, Tyr3→His, Glu4→Ile, Asn5→Ser, and Pro7→Ala) compared with human NT. A peptide with identical chromatographic properties was identified in an extract of frog brain. Synthetic frog NT produced a concentration-dependent increase in αMSH release from perifused frog pars intermedia cells, with an ED50 of 5 × 10−9 m. A maximum response (276.3 ± 45.5% above basal release) was produced by a 10−8-m concentration. Repeated administration of NT to melanotrope cells revealed the occurrence of a rapid and pronounced desensitization mechanism. The data are consistent with a possible role for the peptide as a hypophysiotropic factor in amphibians.

/pdf/isolation-primary-structure-and-effects-on-alpha-melanocyte-4oi6yi7hbi.pdf

J. Michael Conlon

Papers

Characterization and distribution of neuropeptide Y in the brain of a caecilian amphibian.

Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: Potent activity against oral pathogens

Molecular Evolution of Somatostatin Genes

Receptor binding profile of neuropeptide γ and its fragments: Comparison with the nonmammalian peptides carassin and ranakinin at three mammalian tachykinin receptors

Isolation, primary structure, and effects on alpha-melanocyte-stimulating hormone release of frog neurotensin.