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Peptidomic Analysis of Skin Secretions of the Caribbean Frogs Leptodactylus insularum and Leptodactylus nesiotus (Leptodactylidae) Identifies an Ocellatin with Broad Spectrum Antimicrobial Activity
Antibiotics ( IF 4.8 ) Pub Date : 2020-10-20 , DOI: 10.3390/antibiotics9100718
Gervonne Barran , Jolanta Kolodziejek , Laurent Coquet , Jérôme Leprince , Thierry Jouenne , Norbert Nowotny , J. Michael Conlon , Milena Mechkarska

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.

中文翻译:

加勒比海蛙Insularum和Neptodactylus nesiotus(Leptodactylidae)皮肤分泌物的肽组学分析鉴定出具有广谱抗菌活性的Ocellatin。

Ocellatins是在蛙皮中产生的肽,属于Leptodactylus属,通常仅对革兰氏阴性菌显示弱的抗菌活性。从特立尼达州伊卡科斯半岛收集的insularum Leptodactylus insularum Barbour 1906和nesepto Lactodactylus nesiotus Heyer 1994的去甲肾上腺素刺激的皮肤分泌物的肽组分析,导致了从Insularum L. insularum(ocellatin-1I和ocellatin-1I一起)纯化的五个与卵磷脂相关的肽和结构表征。其(1–16)片段,ocellatin-2I及其(1–16)片段和ocellatin-3I)和四种来自奈瑟球菌的ocellatins(ocellatin-1N,-2N,-3N和-4N)。尽管ocellatins-1I,-2I和-1N对革兰氏阴性菌的抗菌效力通常较低,但ocellatin-3N(GIFDVLKNLAKGVITSLAS.NH 2)对耐肺炎克雷伯菌的菌株和大肠埃希菌的参考菌株具有活性。肺炎克雷伯菌铜绿假单胞菌鼠伤寒沙门氏菌(最小抑菌浓度(MIC)在31.25–62.5μM范围内),并且是唯一对革兰氏阳性金黄色葡萄球菌(MIC = 31.25μM)和粪肠球菌有活性的肽(MIC = 62.5μM)。ocellatin-3N对小鼠红细胞的中等溶血活性(LC 50 = 98μM)限制了其治疗潜力。该肽代表设计用于靶向多药耐药病原体的长效,无毒和广谱抗菌剂的模板。
更新日期:2020-10-20
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