Characterization of the Antimicrobial Peptide Penisin, a Class Ia Novel Lantibiotic from Paenibacillus sp Strain A3
Characterization of the Antimicrobial Peptide Penisin, a Class Ia Novel Lantibiotic from Paenibacillus sp Strain A3
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DOI：
10.1128/aac.01813-15
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发表时间：
2016-01-01
影响因子：
4.9
通讯作者：
Korpole, Suresh
中科院分区：
文献类型：
--
作者：
Baindara, Piyush;Chaudhry, Vasvi;Korpole, Suresh
从微生物来源中分离新型抗微生物肽的尝试最近一直在增加，尽管它们在治疗应用中的功效较低。在这里，我们报告了一种新的有效的抗菌肽的鉴定和表征，从细菌菌株命名为A3，表现出最高的身份与类芽孢杆菌爱媛。在纯化和随后的分子表征的抗菌肽，被称为penisin，我们发现的肽是细菌素样肽。与这些结果一致，整个基因组序列的RAST分析揭示了lantibiotic基因簇的存在，该基因簇含有lantibiotic合成和成熟所必需的基因。虽然圆二色性和一维核磁共振实验证实了肽的无规卷曲结构，类似于其他已知的羊毛硫抗生素，但其他生化证据表明核心肽的翻译后修饰产生六个硫醚交联。推测的生物合成基因佩纳的氨基酸序列与elgicin A的相似性约为74%，与lantibiotic paenicidin A的相似性约为50%。青霉素有效地杀死耐甲氧西林金黄色葡萄球菌（MRSA），并没有表现出溶血活性。与其他羊毛硫抗生素不同，它能有效抑制革兰氏阴性菌的生长。此外，80 mg/kg体重的penisin显著降低了小鼠大腿感染模型中的细菌负荷，并在需要感染金黄色葡萄球菌MTCC 96的菌血症模型中保护了BALB/c小鼠，这表明它可能是一种有前途的新的抗微生物肽。
Attempts to isolate novel antimicrobial peptides from microbial sources have been on the rise recently, despite their low efficacy in therapeutic applications. Here, we report identification and characterization of a new efficient antimicrobial peptide from a bacterial strain designated A3 that exhibited highest identity with Paenibacillus ehimensis. Upon purification and subsequent molecular characterization of the antimicrobial peptide, referred to as penisin, we found the peptide to be a bacteriocin-like peptide. Consistent with these results, RAST analysis of the entire genome sequence revealed the presence of a lantibiotic gene cluster containing genes necessary for synthesis and maturation of a lantibiotic. While circular dichroism and one-dimension nuclear magnetic resonance experiments confirmed a random coil structure of the peptide, similar to other known lantibiotics, additional biochemical evidence suggests posttranslational modifications of the core peptide yield six thioether cross-links. The deduced amino acid sequence of the putative biosynthetic gene penA showed approximately 74% similarity with elgicin A and 50% similarity with the lantibiotic paenicidin A. Penisin effectively killed methicillin-resistant Staphylococcus aureus (MRSA) and did not exhibit hemolysis activity. Unlike other lantibiotics, it effectively inhibited the growth of Gram-negative bacteria. Furthermore, 80 mg/kg of body weight of penisin significantly reduced bacterial burden in a mouse thigh infection model and protected BALB/c mice in a bacteremia model entailing infection with Staphylococcus aureus MTCC 96, suggesting that it could be a promising new antimicrobial peptide.