Glycocode-guided bacteriophage-host interaction in the evolution of the genus Staphylococcus

葡萄球菌属进化中糖码引导的噬菌体-宿主相互作用

• 批准号: 465126486
• 负责人: Professor Dr. Andreas Peschel
• 金额: --
• 依托单位: Lehrstuhl für Infektionsbiologie
• 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/465126486?language=en
• 关键词: Glycocode; guided; bacteriophage; host; interaction

The various Staphylococcus species encounter a huge variety of phages in their natural habitats, the human nasal cavity and skin. Being susceptible to specific phages has its ‘pros and cons’ – it governs the vulnerability to phage killing but also the access to a common genetic pool of a species because phages are the major vehicle of horizontal gene transfer in staphylococci. Indeed, the ongoing evolution of new antibiotic resistance, virulence, and fitness traits of the genus is governed by transducing phages. We found that Staphylococcus aureus and Staphylococcus epidermidis alter the species- and strain-specific structure of wall teichoic acid (WTA) glycopolymers at the bacterial surface to shape the susceptibility to specific phages. WTA glycosylation by different hexoses turned out to be particular crucial for binding of specific phage groups and staphylococcal genomes differed in sets of WTA glycosyl transferases. We also characterized WTA-binding proteins at phage base plates to elucidate structure-function relationships. We propose to systematically identify and characterize WTA glycosyl transferases of different Staphylococcus species, elucidate their impact on intra- and interspecies horizontal gene transfer, and correlate glycosylation patterns with the structure of corresponding phage binding proteins. These tools will allow us to identify new transducing phages, which can connect the genetic pools of S. aureus and coagulase-negative staphylococci such as S. epidermidis. Such phages could be responsible for the continuous import of resistance and virulence genes into S. aureus thereby driving the evolution of this major human pathogen. Molecular investigations on the interaction of phage proteins that bind species-specific, glycosylated WTA will yield a comprehensive map of the glycocodes of Staphylococcus-phage interaction with important implications for the ongoing processes of pathogen evolution.

各种葡萄球菌在其自然栖息地，即人类鼻腔和皮肤中遇到了各种各样的细菌。对特定的细菌易感有其“优点和缺点”-它控制着噬菌体杀伤的脆弱性，但也控制着一个物种的共同基因库，因为细菌是葡萄球菌中水平基因转移的主要载体。事实上，正在进行的新的抗生素耐药性，毒力和健身性状的属是由转导基因。我们发现金黄色葡萄球菌和表皮葡萄球菌改变了细菌表面壁磷壁酸（WTA）糖聚合物的种属和菌株特异性结构，从而形成对特异性细菌的易感性。事实证明，不同己糖的WTA糖基化对于特定噬菌体群和WTA糖基转移酶组中不同的葡萄球菌基因组的结合特别重要。我们还在噬菌体基板上表征了WTA结合蛋白，以阐明结构-功能关系。我们建议系统地识别和表征WTA糖基转移酶的不同葡萄球菌属物种，阐明它们对种内和种间水平基因转移的影响，并将糖基化模式与相应的噬菌体结合蛋白的结构相关联。这些工具将使我们能够识别新的转导位点，它可以连接S。金黄色葡萄球菌和凝固酶阴性葡萄球菌如S.表皮此类噬菌体可能负责将抗性和毒力基因持续输入S。金黄色葡萄球菌，从而推动这种主要的人类病原体的进化。对结合物种特异性、糖基化WTA的噬菌体蛋白相互作用的分子研究将产生葡萄球菌-噬菌体相互作用糖码的全面图谱，这对病原体进化的持续过程具有重要意义。