TY - JOUR
T1 - Peptidomic analysis of skin secretions of the caribbean frogs leptodactylus insularum and leptodactylus nesiotus (Leptodactylidae) identifies an ocellatin with broad spectrum antimicrobial activity
AU - Barran, Gervonne
AU - Kolodziejek, Jolanta
AU - Coquet, Laurent
AU - Leprince, Jérôme
AU - Jouenne, Thierry
AU - Nowotny, Norbert
AU - Conlon, J. Michael
AU - Mechkarska, Milena
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10
Y1 - 2020/10
N2 - Ocellatins are peptides produced in the skins of frogs belonging to the genus Leptodactylus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Leptodactylus insularum Barbour 1906 and Leptodactylus nesiotus Heyer 1994, collected in the Icacos Peninsula, Trinidad, led to the purification and structural characterization of five ocellatin-related peptides from L. insularum (ocellatin-1I together with its (1-16) fragment, ocellatin-2I and its (1-16) fragment, and ocellatin-3I) and four ocellatins from L. nesiotus (ocellatin-1N, -2N, -3N, and -4N). While ocellatins-1I, -2I, and -1N showed a typically low antimicrobial potency against Gram-negative bacteria, ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH2) was active against an antibiotic-resistant strain of Klebsiella pneumoniae and reference strains of Escherichia coli, K. pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium (minimum inhibitory concentrations (MICs) in the range 31.25-62.5 μM), and was the only peptide active against Gram-positive Staphylococcus aureus (MIC = 31.25 μM) and Enterococcus faecium (MIC = 62.5 μM). The therapeutic potential of ocellatin-3N is limited by its moderate hemolytic activity (LC50 = 98 μM) against mouse erythrocytes. The peptide represents a template for the design of long-acting, non-toxic, and broad-spectrum antimicrobial agents for targeting multidrug-resistant pathogens.
AB - Ocellatins are peptides produced in the skins of frogs belonging to the genus Leptodactylus that generally display weak antimicrobial activity against Gram-negative bacteria only. Peptidomic analysis of norepinephrine-stimulated skin secretions from Leptodactylus insularum Barbour 1906 and Leptodactylus nesiotus Heyer 1994, collected in the Icacos Peninsula, Trinidad, led to the purification and structural characterization of five ocellatin-related peptides from L. insularum (ocellatin-1I together with its (1-16) fragment, ocellatin-2I and its (1-16) fragment, and ocellatin-3I) and four ocellatins from L. nesiotus (ocellatin-1N, -2N, -3N, and -4N). While ocellatins-1I, -2I, and -1N showed a typically low antimicrobial potency against Gram-negative bacteria, ocellatin-3N (GIFDVLKNLAKGVITSLAS.NH2) was active against an antibiotic-resistant strain of Klebsiella pneumoniae and reference strains of Escherichia coli, K. pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium (minimum inhibitory concentrations (MICs) in the range 31.25-62.5 μM), and was the only peptide active against Gram-positive Staphylococcus aureus (MIC = 31.25 μM) and Enterococcus faecium (MIC = 62.5 μM). The therapeutic potential of ocellatin-3N is limited by its moderate hemolytic activity (LC50 = 98 μM) against mouse erythrocytes. The peptide represents a template for the design of long-acting, non-toxic, and broad-spectrum antimicrobial agents for targeting multidrug-resistant pathogens.
KW - Antibiotic resistance
KW - Antimicrobial peptides
KW - Frog skin secretions
KW - Hemolysis
KW - Leptodactylus
KW - Norepinephrine stimulation
KW - Ocellatins
KW - Peptidomic analysis
KW - Phylogenetics
KW - Trinidad
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U2 - 10.3390/antibiotics9100718
DO - 10.3390/antibiotics9100718
M3 - Article
C2 - 33092132
AN - SCOPUS:85093958350
SN - 2079-6382
VL - 9
SP - 1
EP - 15
JO - Antibiotics
JF - Antibiotics
IS - 10
M1 - 718
ER -