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.

Figure 1

Primary structures of the magainin peptides isolated from skin secretions of frogs belonging to the genera Xenopus and Silurana. The amino acid sequence of magainin-ST1 was deduced from the corresponding nucleotide sequence of genomic DNA. In order to maximize structural similarity, gaps denoted by * have been introduced into some sequences. Strongly conserved residues are shaded.

Figure 2

Primary structures of the peptide glycine-leucine-amide (PGLa) peptides isolated from skin secretions of frogs belonging to the genera Xenopus and Silurana. ^a denotes C-terminal α-amidation. In order to maximize structural similarity, gaps denoted by * have been introduced into some sequences. Strongly conserved residues are shaded.

Figure 3

Primary structures of the caerulein precursor fragment (CPF) peptides isolated from skin secretions of frogs belonging to the genera Xenopus and Silurana. ^a denotes C-terminal α-amidation. In order to maximize structural similarity, gaps denoted by * have been introduced into some sequences. Strongly conserved residues are shaded.

Figure 4

Primary structures of the xenopsin precursor fragment (XPF) peptides isolated from skin secretions of frogs belonging to the genera Xenopus and Silurana. In order to maximize structural similarity, gaps denoted by * have been introduced into some sequences. Strongly conserved residues are shaded.

Figure 5

Primary structures of the hymenochirins isolated from skin secretions of the frogs Hymenochirus boettgeri and Pseudhymenochirus merlini, and the pseudhymenochirins from P. merlini. ^a denotes C-terminal α-amidation. Strongly conserved residues are shaded.