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.
Highlights
The emergence in all regions of the World of strains of pathogenic bacteria and fungi with resistance to commonly used antibiotics constitutes a serious threat to public health and has necessitated a search for novel types of antimicrobial agent to which the microorganisms have not been exposed
It has been suggested that cutaneous symbiotic bacteria may provide the major system of defense against pathogenic microorganisms in the environment with antimicrobial peptides assuming a supplementary role in some species [2]
The ten tetraploid Xenopus species have been divided into three species groups on the basis of similarities in morphology, advertisement calls, and/or nucleotide sequences of mitochondrial genes: the laevis group includes X. laevis, X. gilli, X. largeni, X. petersii, and X. victorianus; the muelleri group includes X. muelleri, X. borealis, and X. clivii; and the fraseri group includes X. fraseri and X. pygmaeus [14,21]
Summary
The emergence in all regions of the World of strains of pathogenic bacteria and fungi with resistance to commonly used antibiotics constitutes a serious threat to public health and has necessitated a search for novel types of antimicrobial agent to which the microorganisms have not been exposed. Skin secretions from many species of Anura (frogs and toads) contain cytotoxic peptides, often in very high concentrations, with broad-spectrum antibacterial and antifungal activities and the ability to permeabilize mammalian cells [2,3]. It has been suggested that cutaneous symbiotic bacteria may provide the major system of defense against pathogenic microorganisms in the environment with antimicrobial peptides assuming a supplementary role in some species [2]. Frog skin host-defense peptides vary in size from as small as eight up to 63 amino acid residues. The frog skin host-defense peptides may be grouped together in sets or families on the basis of limited similarities in amino acid sequence. A major obstacle to the development of frog skin peptides as therapeutically valuable anti-infective agents, if they are to be administered systemically, is their varying degrees of cytotoxicity to mammalian cells and their short-lives in the circulation. This review will examine possible clinical application of well characterized peptides that have been isolated from skin secretions from African clawed frogs belonging to the family Pipidae together with analogs of the naturally occurring peptides that show improved therapeutic potential
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