Antimicrobial peptides isolated from skin secretions of the diploid frog, Xenopus tropicalis (Pipidae)

Mohamed F. Ali, Ana Maria Soto, Floyd C. Knoop, J. Michael Conlon

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Abstract

Seven peptides (XT-1-XT-7) with antimicrobial activity were isolated from norepinephrine-stimulated skin secretions of the diploid clawed frog, Xenopus tropicalis. Structural characterization of the peptides demonstrated that amino acid sequence similarity to antimicrobial peptides previously isolated from Xenopus laevis was low, suggesting that the species are not closely related phylogenetically. Peptides XT-5 and XT-3 are probably the orthologs of X. laevis peptide glycine-leucine amide (PGLa) and the N-terminal spacer region of prolevitide, respectively. XT-1, XT-6 and XT-7 show limited structural similarity to the spacer region of X. laevis procaeruleins and the paralogs XT-2 and XT-4 are similar to corresponding regions of proxenopsin. Orthologs of the magainins were not identified. The C-terminally α-amidated peptide XT-7 (GLLGPLLKIAAKVGSNLL.NH2) showed the lowest minimum inhibitory concentrations against reference microorganisms (Staphylococcus aureus 5 μM, Escherichia coli 5 μM, and Candida albicans 40 μM) and was also active against clinical isolates of methicillin-resistant S. aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus group C, Shigella sonnei, Pseudomonas aeruginosa and Enterobacter cloacae. The peptide was, however, hemolytic against human erythrocytes (50% lysis at 70 μM). Circular dichroism studies showed that XT-7 has a random structure in aqueous solution, pH 7.0 but adopts an α-helical conformation in the presence of 50% trifluoroethanol. Decreasing the cationicity of XT-7 either by replacement of the C-terminal CONH2 group by COOH or by deletion of the Lys8 residue produced analogs with greatly (>10-fold) decreased antimicrobial potencies.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Volume1550
Issue number1
DOIs
StatePublished - Nov 26 2001

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

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