title: Esculentin 1-21: a linear antimicrobial peptide from frog skin with inhibitory effect on bovine mastitis-causing bacteria.
abstract: Mastitis, or inflammation of the mammary gland, is the most common and expensive illness of dairy cows throughout the world. Although stress and physical injuries may give rise to inflammation of the udders, infections by bacteria or other microorganisms remain the major cause, and infusion of antibiotics is the main treatment approach. However, the increased emergence of multidrug-resistant pathogens and the production of milk contaminated with antibiotics has become a serious threat in the livestock. Hence, there is an urgent need for the discovery of new therapeutic agents with a new mode of action. Gene-encoded AMPs, which represent the first line of defence in all living organisms, are considered as promising candidates for the development of new anti-infective agents. This paper reports on the antibacterial activities in vitro and in an animal model, of the frog skin AMP esculentin 1-21 [Esc(1-21)], along with a plausible mode of action. Our data revealed that this peptide (i) is highly potent against the most common mastitis-causing microbes (e.g. Streptococcus agalactiae); and (ii) is active in vivo, causing a visible regression of the clinical stage of mastitis in dairy cows, after 1 week of peptide treatment. Biophysical characterisation revealed that the peptide adopts an alpha-helical structure in microbial mimicking membranes and is able to permeate the membrane of S. agalactiae in a dose-dependent manner. Overall, these data suggest Esc(1-21) as an attractive AMP for the future design of new antibiotics to cure mastitis in cattle.
authors.affiliation: Laboratorio de Péptidos Naturales, Departamento de Biología Celular y Molecular, Universidad de Guadalajara, Centro Universitario de Ciencias Biológicas y Agropecuarias, Zapopan, Jalisco, México.
authors.forename: Alfonso Enrique
authors.initials: AE
authors.lastname: Islas-Rodrìguez
authors.forename: Ludovica
authors.initials: L
authors.lastname: Marcellini
authors.forename: Barbara
authors.initials: B
authors.lastname: Orioni
authors.forename: Donatella
authors.initials: D
authors.lastname: Barra
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Stella
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
mesh_terms: D029845:Amphibian Proteins / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001001:Anura; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008414:Mastitis, Bovine / Q000382:microbiology*
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; C092874:esculentin protein, Rana esculenta