Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage
Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage
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DOI：
10.1371/journal.ppat.1008314
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发表时间：
2020-02-01
期刊：
影响因子：
6.7
通讯作者：
Dokland, Terje
中科院分区：
文献类型：
--
作者：
Kizziah, James L.;Manning, Keith A.;Dokland, Terje
金黄色葡萄球菌是人类感染的常见原因。出现了毒性，抗药性菌株的S。金黄色葡萄球菌是重要的公共卫生问题。大多数毒力因子和抗性因子都是S.金黄色葡萄球菌是由移动的遗传元件编码的，并且噬菌体的转导代表了水平基因转移的主要机制。底板是噬菌体尾部尖端的一种特殊结构，在宿主识别、细胞壁穿透和DNA排出中起关键作用。我们用高分辨率冷冻电子显微镜来确定S。金黄色葡萄球菌噬菌体80 α基板在3.75埃的分辨率，允许原子模型，以建立大多数主要的尾巴和基板蛋白，包括两个尾纤维，受体结合蛋白，和卷尺蛋白的一部分。我们的结构提供了一个结构基础，了解宿主识别，细胞壁渗透和DNA喷射病毒感染革兰氏阳性菌。与其他噬菌体的比较表明了基板蛋白的模块化设计，以及葡萄球菌和其他病原体进化过程中对宿主的适应。作者总结对大多数抗生素具有耐药性的金黄色葡萄球菌强毒株的出现已成为一个主要的公共卫生问题。S.金黄色葡萄球菌通常携带在移动的遗传元件（MGE）上。噬菌体的转导是MGE在细菌群体中水平传播的主要途径，因此对沙门氏菌致病性的进化至关重要。金黄色葡萄球菌和其他病原体。基板是位于噬菌体尾部尖端的复杂结构，具有多种作用，包括宿主识别和结合、细胞壁穿透以及噬菌体DNA的排出。我们已经确定了来自噬菌体80 α的基板的结构，噬菌体80 α是参与宿主致病性和S.金黄色。我们的结构提供了一个基础，了解宿主的识别和感染的细菌感染革兰氏阳性宿主，以及在细菌致病性的进化过程中发生的适应。了解这些过程对于开发基于噬菌体的策略来对抗沙门氏菌的抗生素耐药性将是重要的。金黄色。
Staphylococcus aureus is a common cause of infections in humans. The emergence of virulent, antibiotic-resistant strains of S. aureus is a significant public health concern. Most virulence and resistance factors in S. aureus are encoded by mobile genetic elements, and transduction by bacteriophages represents the main mechanism for horizontal gene transfer. The baseplate is a specialized structure at the tip of bacteriophage tails that plays key roles in host recognition, cell wall penetration, and DNA ejection. We have used high-resolution cryo-electron microscopy to determine the structure of the S. aureus bacteriophage 80 alpha baseplate at 3.75 angstrom resolution, allowing atomic models to be built for most of the major tail and baseplate proteins, including two tail fibers, the receptor binding protein, and part of the tape measure protein. Our structure provides a structural basis for understanding host recognition, cell wall penetration and DNA ejection in viruses infecting Gram-positive bacteria. Comparison to other phages demonstrates the modular design of baseplate proteins, and the adaptations to the host that take place during the evolution of staphylococci and other pathogens.Author summaryThe emergence of virulent strains of Staphylococcus aureus that are resistant to most antibiotics has become a major public health concern. Virulence and resistance determinants in S. aureus are usually carried on mobile genetic elements (MGEs). Transduction by bacteriophages provides the main means by which MGEs are disseminated horizontally through the bacterial population, and is therefore essential to the evolution of pathogenicity of S. aureus and other pathogens. The baseplate is a complex structure at the tip of bacteriophage tails that serves multiple roles, including host recognition and binding, cell wall penetration, and ejection of the phage DNA. We have determined the structure of the baseplate from bacteriophage 80 alpha, a representative of phages involved in host pathogenicity and in the mobilization of MGEs in S. aureus. Our structure provides a basis for understanding host recognition and infection by phages infecting Gram-positive hosts, and the adaptations that take place during evolution of bacterial pathogenicity. An understanding of these processes will be important to develop phage-based strategies for combatting antibiotic resistance in S. aureus.