Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, 17666 Al-Ain, United Arab Emirates.
Peptides. 2012 Sep;37(1):113-9. doi: 10.1016/j.peptides.2012.07.005. Epub 2012 Jul 16.
A putative genome duplication event within the Silurana lineage has given rise to the tetraploid Cameroon clawed frog Silurana epitropicalis (Fischberg, Colombelli, and Picard, 1982). Peptidomic analysis of norepinephrine-stimulated skin secretions of S. epitropicalis led to identification of 10 peptides with varying degrees of growth-inhibitory activity against Escherichia coli and Staphylococcus aureus. Structural characterization identified the peptides as belonging to the magainin family (magainin-SE1), the caerulein-precursor fragment family (CPF-SE1, -SE2 and -SE3), the xenopsin-precursor fragment family (XPF-SE1, SE-2, SE-3 and -SE4), and the peptide glycine-leucine-amide family (PGLa-SE1 and -SE2). In addition, peptide phenylalanine-glutamine-amide (FLGALLGPLMNLLQ·NH(2)) was isolated from the secretions that lacked antimicrobial activity. Comparison of the multiplicity of orthologous peptides in S. epitropicalis and the diploid Silurana tropicalis indicates that extensive nonfunctionalization (deletion or silencing) of antimicrobial peptide genes has occurred after polyploidization in the Silurana lineage, as in the Xenopus lineage. CPF-SE2 (GFLGPLLKLGLKGAAKLLPQLLPSRQQ; MIC=2.5μM) and CPF-SE3 (GFLGSLLKTGLKVGSNLL·NH(2); MIC=5μM) showed potent growth-inhibitory activity against a range of clinical isolates of methicillin-resistant S. aureus (MRSA). Their utility as systemic anti-infective drugs is limited by significant hemolytic activity against human erythrocytes (LC(50)=50μM for CPF-SE2 and 220μM for CPF-SE3) but the peptides may find application as topical agents in treatment of MRSA skin infections and decolonization of MRSA carriers.
在 Silurana 谱系中发生的假定基因组加倍事件导致了四倍体喀麦隆爪蟾 Silurana epitropicalis（Fischberg、Colombelli 和 Picard，1982）的出现。对 Silurana epitropicalis 受去甲肾上腺素刺激的皮肤分泌物进行的肽组学分析导致鉴定出 10 种具有不同程度抑制大肠杆菌和金黄色葡萄球菌生长活性的肽。结构特征鉴定这些肽属于防御素家族（magainin-SE1）、蛙皮素前体片段家族（CPF-SE1、-SE2 和 -SE3）、章鱼胺前体片段家族（XPF-SE1、SE-2、SE-3 和 -SE4）和肽甘氨酸-亮氨酸酰胺家族（PGLa-SE1 和 -SE2）。此外，从缺乏抗菌活性的分泌物中分离出肽苯丙氨酸-谷氨酰胺酰胺（FLGALLGPLMNLLQ·NH(2)）。Silurana epitropicalis 中同源肽的多样性比较和二倍体 Silurana tropicalis 表明，在 Silurana 谱系中的多倍化之后，抗菌肽基因发生了广泛的非功能化（缺失或沉默），就像在 Xenopus 谱系中一样。CPF-SE2（GFLGPLLKLGLKGAAKLLPQLLPSRQQ；MIC=2.5μM）和 CPF-SE3（GFLGSLLKTGLKVGSNLL·NH(2)；MIC=5μM）对一系列耐甲氧西林金黄色葡萄球菌（MRSA）的临床分离株表现出强烈的生长抑制活性。它们作为全身性抗感染药物的用途受到对人红细胞有显著溶血活性的限制（CPF-SE2 的 LC(50)=50μM，CPF-SE3 的 LC(50)=220μM），但这些肽可能作为治疗 MRSA 皮肤感染和 MRSA 携带者去定植的局部制剂应用。
