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温和噬菌体的特异性整合降低了宿主细菌的致病性。

Specific Integration of Temperate Phage Decreases the Pathogenicity of Host Bacteria.

机构信息

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China.

出版信息

Front Cell Infect Microbiol. 2020 Feb 4;10:14. doi: 10.3389/fcimb.2020.00014. eCollection 2020.

Abstract

Temperate phages are considered as natural vectors for gene transmission among bacteria due to the ability to integrate their genomes into a host chromosome, therefore, affect the fitness and phenotype of host bacteria. Many virulence genes of pathogenic bacteria were identified in temperate phage genomes, supporting the concept that temperate phages play important roles in increasing the bacterial pathogenicity through delivery of the virulence genes. However, little is known about the roles of temperate phages in attenuation of bacterial virulence. Here, we report a novel temperate phage, vB_BbrS_PHB09 (PHB09), which has a 42,129-bp dsDNA genome with a G+C content of 62.8%. Phylogenetic analysis based on large terminase subunit indicated that phage PHB09 represented a new member of the family Siphoviridae. The genome of PHB09 contains genes encoding lysogen-associated proteins, including integrase and cI protein. The integration site of PHB09 is specifically located within a pilin gene of . Importantly, we found that the integration of phage PHB09 significantly decreased the virulence of parental strain Bb01 in mice, most likely through disruption the expression of pilin gene. Moreover, a single shot of the prophage bearing strain completely protected mice against lethal challenge with wild-type virulent , indicating the vaccine potential of lysogenized strain. Our findings not only indicate the complicated roles of temperate phages in bacterial virulence other than simple delivery of virulent genes but also provide a potential strategy for developing bacterial vaccines.

摘要

温和噬菌体被认为是细菌基因传递的天然载体,因为它们能够将其基因组整合到宿主染色体中,从而影响宿主细菌的适应性和表型。许多病原菌的毒力基因都在温和噬菌体基因组中被鉴定出来,这支持了温和噬菌体通过传递毒力基因在增加细菌致病性方面发挥重要作用的概念。然而,关于温和噬菌体在减弱细菌毒力方面的作用知之甚少。在这里,我们报告了一种新型温和噬菌体 vB_BbrS_PHB09(PHB09),它具有一个 42129 碱基对的双链 DNA 基因组,GC 含量为 62.8%。基于大型终止酶亚基的系统发育分析表明,噬菌体 PHB09 代表了肌尾噬菌体科的一个新成员。PHB09 基因组包含编码溶原相关蛋白的基因,包括整合酶和 cI 蛋白。PHB09 的整合位点专门位于 pilin 基因内。重要的是,我们发现噬菌体 PHB09 的整合显著降低了亲本菌株 Bb01 在小鼠中的毒力,这很可能是通过破坏 pilin 基因的表达来实现的。此外,单次注射携带噬菌体的菌株完全保护小鼠免受野生型强毒菌株的致命攻击,表明溶原化菌株具有疫苗潜力。我们的研究结果不仅表明温和噬菌体在细菌毒力中的作用比简单传递毒力基因更为复杂,而且为开发细菌疫苗提供了一种潜在的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6058/7010805/16999bd09630/fcimb-10-00014-g0001.jpg

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