Caerulein precursor fragment 3 skin#
laevis skin toxin caerulein (Cae) and its cosecreted antimicrobial peptide, caerulein precursor fragment (CPF). Note the defensive skin secretion (black arrow), known to contain toxins (including caerulein) and AMPs (photograph taken by Jannie Smit). a Litoria caerulea (an Australian tree frog) attacked by the snake Dendrelaphis punctulatus. Upon receptor binding, these toxins essentially simulate an overdose of a predator’s hormone or neuropeptide, resulting in a range of adverse effects, including nausea, hypotension, and hyperalgesia 3, 7, 9, 10.Ī frog antimicrobial peptide promotes the transepithelial passage of a cosecreted toxin. These toxins generally resemble vertebrate hormones or neuropeptides and undergo posttranslational modifications that increase their lifespan in a predator’s bloodstream or enhance their affinity to a target receptor 8, 9, 10. Many frog species however, secrete much larger molecules with systemic targets, like peptides (typically 0.5–2 kDa) and in some cases even small proteins (4–8 kDa) 3, 4, 5, 6, 7. In the absence of structures that create a wound to inject toxins, fast delivery is typically only possible for small molecules (<300 Da) that are easily absorbed through oral epithelia, like cyanides, alkaloids, or steroids 1, 2. To achieve this, animals may produce toxins with immediate local effects, like pain or distastefulness, or molecules with systemic effects that rely on fast infiltration into a predator’s body 1. aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDRAB) with MIC values in the range 4–8 μM.When a poisonous or venomous animal is attacked by a predator, it usually has little time to deploy its toxins and induce a response in the aggressor to avoid being killed (Fig. CPF-B1 was active against clinical isolates of the nosocomial pathogens, methicillin-resistant S. This peptide was also the most abundant antimicrobial peptide in the skin secretions. aureus, and MIC = 25 μM against Candida albicans, and low hemolytic activity against human erythrocytes (LC50 > 200 μM). The peptide with the greatest potential for development into a therapeutically valuable anti-infective agent was CPF-B1 (GLGSLLGKAFKIGLKTVGKMMGGAPREQ) with MIC = 5 μM against E. In addition, a second magainin-related peptide (G**KFLHSAGKFGKAFLGEVMIG) containing a two amino acid residue deletion compared with magainin-2 was identified that had only weak antimicrobial activity. Structural characterization of the peptides demonstrated that they were orthologous to magainin-2 (1 peptide), peptide glycine–leucine-amide, PGLa (2 peptides), caerulein-precursor fragments, CPF (4 peptides), and xenopsin-precursor fragments, XPF (2 peptides), previously isolated from Xenopus laevis and X. Nine peptides with differential growth inhibitory activity against Escherichia coli and Staphylococcus aureus were isolated from norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus borealis Parker, 1936 (Pipidae). While the production of dermal cytolytic peptides may offer definite evolutionary advantage to anurans, their precise biological function, for example during metamorphosis, may need to be re-evaluated. Although cytolytic activity against the chytrid fungus Batrachochytrium dendrobatidis, responsible for anuran population declines worldwide, has been demonstrated in vitro, the ability of frog skin antimicrobial peptides to protect the animal in the wild appears to be limited. At this time, antimicrobial peptides have been identified in the skin of frogs from species belonging to the Bombinatoridae, Hylidae, Hyperoliidae, Leiopelmatidae, Leptodactylidae, Myobatrachidae, Pipidae, and Ranidae families, but several well-studied species from the Bufonidae, Ceratophryidae, Dicroglossidae, Microhylidae, Pelobatidae, Pyxicephalidae, Rhacophoridae, and Scaphiopodidae families do not appear to synthesize these peptides.
However, the importance of the peptides in the survival strategy of the animal is not clearly understood. These peptides frequently display potent cytolytic activities against a range of pathogenic bacteria and fungi, consistent with the hypothesis that they play a role in host defense. Cationic peptides with the propensity to adopt an amphipathic alpha-helical conformation in a membrane-mimetic environment are synthesized in the skin of many species of frogs.
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