细菌表面寄生菌TM7x帮助宿主菌逃避噬菌体捕获的机制研究

Bacteriophage resistance mechanism is a very rewarding research field. It not only revealed many biological mechanisms of bacterial resistances to phages, but also led to the discovery of revolutionary technologies in life sciences, such as restrictive enzymes and Crispr/Cas system. However, all the current phage resistance mechanisms are based on the individual bacteriophage and bacterium. In nature, such as the oral and intestinal tract, there are complex parasitic, symbiotic and competitive relationships between bacteria. At present, it is not clear that the effect of bacterium-bacterium interactions on phage resistance. PNAS recently reported a "non-cultivable" bacterium TM7x, which lives on the surface of host strain Actinomyces odontolyticus XH001. TM7x is an epibiotic parasitic bacterium and cannot replicate independently. We isolated a lytic phage LC001 which infects XH001. Unexpectedly, TM7x can protect the host XH001 from phage adsorption and infection. Therefore, we aim to use genetic, biochemical and morphological techniques to identify the receptor of phage LC001, and then study the effect of TM7x on the bacteriophage receptor on the surface of host bacteria. In summary, we will identify the molecular mechanisms through which TM7x protects its host from phage predation. The study is expected to reveal a novel phage resistance mechanism, and provide new ideas for the study of oral phage biology and phage resistance mechanism.

噬菌体耐受机制是一个成果丰硕的研究领域，揭示了众多细菌耐受噬菌体的机制，也产生了限制内切酶、CIRSPR/Cas等革命性技术。但是，目前所有的噬菌体耐受机制研究都是基于单个细菌对单个噬菌体的耐受。在自然界中，如口腔和肠道，细菌通常是“群居”的，细菌-细菌之间存在复杂的寄生、共生、竞争关系。目前，还不清楚细菌-细菌之间的相互作用对噬菌体耐受的影响。PNAS近期报道了一株“不可培养”细菌TM7x，它以溶齿放线菌XH001为宿主，寄生于宿主表面，不能独立繁殖。我们以XH001为宿主，分离到一株裂解性噬菌体LC001。意外的发现，TM7x能保护宿主菌XH001不被噬菌体吸附和感染。因此，本课题拟用遗传、生化和形态学等技术，先鉴定噬菌体LC001的受体，进而研究TM7x对宿主菌表面的噬菌体受体的影响，从而阐明TM7x保护宿主菌不被噬菌体感染的分子机制，揭示一种全新的寄生菌介导的噬菌体耐受机制。

噬菌体耐受机制是一个成果丰硕的研究领域，揭示了众多细菌耐受噬菌体的机制，也产生了限制内切酶、CIRSPR/Cas等革命性技术。但是，目前所有的噬菌体耐受机制研究都是基于单个细菌对单个噬菌体的耐受。在自然界中，如口腔和肠道，细菌通常是“群居”的，细菌-细菌之间存在复杂的寄生、共生、竞争关系。目前，还不清楚细菌-细菌之间的相互作用对噬菌体耐受的影响。TM7x是一种口腔中的寄生细菌，它以溶齿放线菌XH001为宿主，寄生于宿主表面，不能独立繁殖。我们以XH001为宿主，分离到一株裂解性噬菌体LC001。意外的发现，TM7x能保护宿主菌XH001不被噬菌体吸附和感染。因此，本课题拟用遗传、生化和形态学等技术，先鉴定噬菌体LC001的受体，进而研究TM7x对宿主菌表面的噬菌体受体的影响，发现TM7x感染XH001后，能下调其多糖合成基因簇的表达，从而阻止噬菌体吸附，而过表达该基因簇，则可以使得噬菌体LC001感染被TM7x吸附的细菌。本研究阐明TM7x保护宿主菌不被噬菌体感染的分子机制，揭示一种全新的寄生菌介导的噬菌体耐受机制。