Molecular cross-talk between Sa3int phages and their Stapylococcus aureus host

Sa3int 噬菌体与其金黄色葡萄球菌宿主之间的分子串扰

• 批准号: 464612409
• 负责人: Professorin Dr. Christiane Wolz
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/464612409?language=en
• 关键词: Molecular; cross; talk; between; Sa3int

As a major opportunistic pathogen of human and animals Staphylococcus aureus asymptomatically colonizes the nasal cavity, but is also a leading cause of life-threatening acute and chronic infections. Evolution of the species as a result of short- and long-term adaptation to diverse hosts is tightly linked to phage-mediated transfer of extra-chromosomal mobile elements as well as chromosomal markers. S. aureus strains can carry up to four temperate phages, many of which possess accessory genes coding for staphylococcal virulence factors. More than 90% of the human nasal isolates of S. aureus were found to carry Sa3int phages, which integrate as prophages into the bacterial hlb gene thus disrupting the expression of the sphingomyelinase Hlb, an important virulence factor under certain infection conditions. Among the virulence factors-encoding genes carried by the ϕSa3-phages are staphylokinase, enterotoxins, chemotaxis-inhibitory proteins, and/or staphylococcal complement inhibitors, all of which are highly human-specific and probably essential for bacterial survival in the human host. Thus, both insertion of the prophages into and excision from the bacterial genome have the potential to confer a fitness advantage to S. aureus. There is now also growing evidence that Sa3int phages might perform “active lysogeny”, a process during which a prophage is temporally excised from the chromosome without forming intact phage particles. However, how the S. aureus host modulates the life cycle of its temperate phages remains largely unknown. Our data suggest that the bacterial factors supposedly involved in the interaction of the bacterial host with its phages are likely to be strain specific, with certain S. aureus strains being more prone than others to support either a lysogenic or a lytic life cycle. We aim to decipher the molecular mechanisms regulating the transition of Sa3int phages from a lysogenic to “active lysogenic” or to the lytic phase. Bioinformatic analyses will give insights into the diversity of Sa3int phages and their linkage to certain S. aureus linages. Phage and bacterial factors involved in the lysogenic-“active lysogenic”-lytic switch will be elucidated and their putative interactions assessed. Lysogeny, “active lysogeny” and lytic phage cycles will be monitored over time on the single cell level using microfluidic devices. This will help us understand how these peculiar phages have evolved together with their bacterial host S. aureus.

金黄色葡萄球菌作为人和动物的主要条件致病菌，无症状地定植于鼻腔，但也是危及生命的急性和慢性感染的主要原因。作为对不同宿主的短期和长期适应的结果的物种进化与噬菌体介导的染色体外移动的元件以及染色体标记的转移紧密相关。S.金黄色葡萄球菌菌株可以携带多达四种的温和致病因子，其中许多具有编码葡萄球菌毒力因子的辅助基因。90%以上的人鼻内分离的S.发现金黄色葡萄球菌携带Sa 3 int β，Sa 3 int β作为前噬菌体整合到细菌HLB基因中，从而破坏鞘磷脂酶HLB（在某些感染条件下的重要毒力因子）的表达。在毒力因子编码基因中，由SA 33-SA 33携带的是葡激酶、肠毒素、趋化性抑制蛋白和/或葡萄球菌补体抑制剂，所有这些都是高度人类特异性的，并且可能是细菌在人类宿主中生存所必需的。因此，将原噬菌体插入细菌基因组和从细菌基因组中切除都有可能赋予S.金黄色的现在也有越来越多的证据表明，Sa 3 int噬菌体可能执行“主动溶原性”，在此过程中，原噬菌体暂时从染色体上切除，而不形成完整的噬菌体颗粒。然而，S.金黄色葡萄球菌宿主调节其温带真菌的生活周期仍然是未知的。我们的数据表明，假定参与细菌宿主与其宿主相互作用的细菌因子可能是菌株特异性的，某些S。金黄色葡萄球菌菌株比其它菌株更倾向于支持溶原性或裂解性生命周期。我们的目标是破译调节Sa 3 int从溶原性到“活性溶原性”或到溶解相的转变的分子机制。生物信息学分析将深入了解Sa 3 int的多样性及其与某些S。金黄色葡萄球菌噬菌体和细菌因子参与溶源性-“主动溶源性”-裂解开关将阐明和他们的假定相互作用进行评估。将使用微流体装置在单细胞水平上随时间监测溶原性、“主动溶原性”和裂解性噬菌体循环。这将有助于我们了解这些奇特的细菌是如何与它们的细菌宿主S一起进化的。金黄色。