Host-Defense Peptides with Therapeutic Potential from Skin Secretions of Frogs from the Family Pipidae

Abstract

Skin secretions from frogs belonging to the genera Xenopus, Silurana, Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of host-defense peptides with varying degrees of antimicrobial activities and cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF) peptides have been isolated from norepinephrine-stimulated skin secretions from several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A major obstacle to the development of these peptides as anti-infective agents is their hemolytic activities against human erythrocytes. Analogs of the magainins, CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low cytotoxicities have been developed that are active (MIC < 5 μM) against multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae. Despite this, the therapeutic potential of frog skin peptides as anti-infective agents has not been realized so that alternative clinical applications as anti-cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored.

Karyological analyses of Pseudhymenochirus merlini and Hymenochirus boettgeri provide new insights into the chromosome evolution in the anuran family Pipidae

“…Members of the former two genera, namely Xenopus laevis (Daudin, 1802) and Silurana tropicalis (Gray, 1864), are model organisms (Cannatella and de Sá, 1993) with the complete DNA sequence of S. tropicalis genome available since 2010 (Hellsten et al, 2010). The two species have been intensively analyzed in different scientific disciplines including developmental biology, morphology, cellular biology, molecular biology, genetics, physiology, and pharmaceutics (Khokha et al, 2002;Grainger, 2012;Irisarri et al, 2011;Conlon and Mechkarska, 2014).…”

Unraveling host-vector-arbovirus interactions by two-gene high resolution melting mosquito bloodmeal analysis in a Kenyan wildlife-livestock interface

“…This kind of feeding could be opportunistic when both amphibians and mosquitoes localize in swampy habitats. Alternatively, such feeding behavior may be restricted to specific mosquito species as some mosquito repellants have been isolated from frog skin [47], and mosquitoes may possibly benefit from antimicrobial peptides found in amphibian skin [48]. This study clearly demonstrates the improved resolution of HRM-based bloodmeal analysis by using two distinct molecular markers, revealing broad opportunistic host feeding patterns among mosquito vectors in arbovirus endemic regions of Kenya.…”

Host-defense peptides of the skin with therapeutic potential: From hagfish to human

“…A number of recent articles have reviewed the species distribution, primary structures, and antimicrobial activities of these compounds [10,26,28,65]. Despite the considerable enthusiasm that accompanied the discovery of the magainins in skin secretion of Xenopus laevis in 1987 [47,132], it is fair to write that the promise of naturally occurring amphibian host-defense as effective anti-infective agents, even for topical applications, has not been fulfilled.…”