Insights into caudate amphibian skin secretions with a focus on the chemistry and bioactivity of derived peptides.

Amphibians are well-known for their ability to produce and secrete a mixture of bioactive substances in specialized skin glands for the purpose of antibiotic self-protection and defense against predators. Some of these secretions contain various small molecules, such as the highly toxic batrachotoxin, tetrodotoxin, and samandarine. For some time, the presence of peptides in amphibian skin secretions has attracted researchers, consisting of a diverse collection of - to the current state of knowledge - three to 104 amino acid long sequences. From these more than 2000 peptides many are known to exert antimicrobial effects. In addition, there are some reports on amphibian skin peptides that can promote wound healing, regulate immunoreactions, and may serve as antiparasitic and antioxidative substances. So far, the focus has mainly been on skin peptides from frogs and toads (Anura), eclipsing the research on skin peptides of the ca. 700 salamanders and newts (Caudata). Just recently, several novel observations dealing with caudate peptides and their structure-function relationships were reported. This review focuses on the chemistry and bioactivity of caudate amphibian skin peptides and their potential as novel agents for clinical applications.

Kröner L ，Lötters S ，Hopp MT 《-》

Peptides Isolated from Amphibian Skin Secretions with Emphasis on Antimicrobial Peptides.

Chen X ，Liu S ，Fang J ，Zheng S ，Wang Z ，Jiao Y ，Xia P ，Wu H ，Ma Z ，Hao L ... -  《Toxins》

Skin glands of an aquatic salamander vary in size and distribution and release antimicrobial secretions effective against chytrid fungal pathogens.

Amphibian skin is unique among vertebrate classes, containing a large number of multicellular exocrine glands that vary among species and have diverse functions. The secretions of skin glands contain a rich array of bioactive compounds including antimicrobial peptides (AMPs). Such compounds are important for amphibian innate immune responses and may protect some species from chytridiomycosis, a lethal skin disease caused by the fungal pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). While the bioactivity of skin secretions against Bd has been assessed for many amphibian taxa, similar studies are lacking for Bsal, a chytrid fungus that is especially pathogenic for salamanders. We studied the skin glands and their potential functions in an aquatic salamander, the three-toed amphiuma (Amphiuma tridactylum). Skin secretions of captive adult salamanders were analyzed by RP-HPLC and tested against the growth of Bd and Bsal using in vitro assays. We found that compounds within collected skin secretions were similar between male and female salamanders and inhibited the growth of Bd and Bsal. Thus, skin secretions that protect against Bd may also provide protection against Bsal. Histological examination of the skin glands of preserved salamanders revealed the presence of enlarged granular glands concentrated within caudal body regions. A site of potential gland specialization was identified at the tail base and may indicate specialized granular glands related to courtship and communication.

Pereira KE ，Crother BI ，Sever DM ，Fontenot CL Jr ，Pojman JA Sr ，Wilburn DB ，Woodley SK ... -  《-》

The importance of antimicrobial peptides (AMPs) in amphibian skin defense.

Antimicrobial peptides (AMPs) are produced for defense in nearly all taxa from simple bacteria to complex mammalian species. Some amphibian families have developed this defensive strategy to a high level of sophistication by loading the AMPs into specialized granular glands within the dermis. Enervated by the sympathetic nervous system, the granular glands are poised to deliver an array of AMPs to cleanse the wound and facilitate healing. There have been a number of excellent review publications in recent years that describe amphibian AMPs with an emphasis on their possible uses for human medicine. Instead, my aim here is to review what is known about the nature of amphibian AMPs, the diversity of amphibian AMPs, regulation of their production, and to provide the accumulated evidence that they do, indeed, play an important role in the protection of amphibian skin, vital for survival. While much has been learned about amphibian AMPs, there are still important gaps in our understanding of peptide synthesis, storage, and functions.

Rollins-Smith LA 《-》

Antimicrobial Peptides: Amphibian Host Defense Peptides.

Antimicrobial Peptides (AMPs) are one of the most common components of the innate immune system that protect multicellular organisms against microbial invasion. The vast majority of AMPs are isolated from the frog skin. Anuran (frogs and toads) skin contains abundant AMPs that can be developed therapeutically. Such peptides are a unique but diverse group of molecules. In general, more than 50% of the amino acid residues form the hydrophobic part of the molecule. Normally, there are no conserved structural motifs responsible for activity, although the vast majority of the AMPs are cationic due to the presence of multiple lysine residues; this cationicity has a close relationship with antibacterial activity. Notably, recent evidence suggests that synthesis of AMPs in frog skin may confer an advantage on a particular species, although they are not essential for survival. Frog skin AMPs exert potent activity against antibiotic-resistant bacteria, protozoa, yeasts, and fungi by permeating and destroying the plasma membrane and inactivating intracellular targets. Importantly, since they do not bind to a specific receptor, AMPs are less likely to induce resistance mechanisms. Currently, the best known amphibian AMPs are esculentins, brevinins, ranacyclins, ranatuerins, nigrocin-2, magainins, dermaseptins, bombinins, temporins, and japonicins-1 and -2, and palustrin-2. This review focuses on these frog skin AMPs and the mechanisms underlying their antimicrobial activity. We hope that this review will provide further information that will facilitate further study of AMPs and cast new light on novel and safer microbicides.

Patocka J ，Nepovimova E ，Klimova B ，Wu Q ，Kuca K ... -  《-》