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首页> 外文期刊>Applied Microbiology >Restoration of Bioactive Lantibiotic Suicin from a Remnant lan Locus of Pathogenic Streptococcus suis Serotype 2
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Restoration of Bioactive Lantibiotic Suicin from a Remnant lan Locus of Pathogenic Streptococcus suis Serotype 2

机译：从残留的致病性猪链球菌血清型2 lan座位恢复生物活性羊毛硫抗生素。

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Lantibiotics are ribosomally synthesized, posttranslationally modified antimicrobial peptides. Their biosynthesis genes are usually organized in gene clusters, which are mainly found in Gram-positive bacteria, including pathogenic streptococci. Three highly virulent Streptococcus suis serotype 2 strains (98HAH33, 05ZYH33, and SC84) have been shown to contain an 89K pathogenicity island. Here, on these islands, we unveiled and reannotated a putative lantibiotic locus designated sui which contains a virulence-associated two-component regulator, suiK-suiR. In silico analysis revealed that the putative lantibiotic modification gene suiM was interrupted by a 7.9-kb integron and that other biosynthesis-related genes contained various frameshift mutations. By reconstituting the intact suiM in Escherichia coli together with a semi- in vitro biosynthesis system, a putative lantibiotic named suicin was produced with bactericidal activities against a variety of Gram-positive strains, including pathogenic streptococci and vancomycin-resistant enterococci. Ring topology dissection indicated that the 34-amino-acid lantibiotic contained two methyllanthionine residues and one disulfide bridge, which render suicin in an N-terminal linear and C-terminal globular shape. To confirm the function of suiK-suiR , SuiR was overexpressed and purified. In vitro analysis showed that SuiR could specifically bind to the suiA gene promoter. Its coexpression with suiK could activate suiA gene promoter in Lactococcus lactis NZ9000. Conclusively, we obtained a novel lantibiotic suicin by restoring its production from the remnant sui locus and demonstrated that virulence-associated SuiK-SuiR regulates its production.
机译：羊毛硫抗生素是核糖体合成的，翻译后修饰的抗菌肽。它们的生物合成基因通常组织在基因簇中，这些簇主要存在于革兰氏阳性细菌中，包括致病性链球菌。三种高毒力猪链球菌2型菌株（98HAH33、05ZYH33和SC84）已显示含有89K致病岛。在这里，我们在这些岛屿上揭开并重新命名了一个推定的羊毛素抗生素基因座，命名为sui，其中包含与毒力相关的两组分调节剂suiK-suiR。在计算机分析中发现，推测的羊毛硫抗生素修饰基因suiM被7.9kb的整合子打断，其他与生物合成相关的基因包含各种移码突变。通过将完整的suiM与半体外生物合成系统一起重建，推定的名为suicin的羊毛硫抗生素被生产出来，具有对多种革兰氏阳性菌株（包括病原性链球菌和耐万古霉素的肠球菌）的杀菌活性。环形拓扑解剖表明，该34个氨基酸的羊毛硫抗生素含有2个甲基羊毛硫氨酸残基和1个二硫键，从而使suicin呈N端线性和C端球形。为了确认suiK-suiR的功能，SuiR被过表达和纯化。体外分析表明SuiR可以特异性结合suiA基因启动子。它与suiK的共表达可以激活乳酸乳球菌NZ9000中的suiA基因启动子。最后，我们通过从残留的sui基因座恢复生产来获得新型羊毛硫抗生素suicin，并证明了与毒力相关的SuiK-SuiR调节着其生产。

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