Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142;
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12277-12282. doi: 10.1073/pnas.1810625115. Epub 2018 Nov 15.
Around one-quarter of bacterial diversity comprises a single radiation with reduced genomes, known collectively as the Candidate Phyla Radiation. Recently, we coisolated TM7x, an ultrasmall strain of the Candidate Phyla Radiation phylum Saccharibacteria, with its bacterial host s strain XH001 from human oral cavity and stably maintained as a coculture. Our current work demonstrates that within the coculture, TM7x cells establish a long-term parasitic association with host cells by infecting only a subset of the population, which stay viable yet exhibit severely inhibited cell division. In contrast, exposure of a naïve s isolate, XH001n, to TM7x cells leads to high numbers of TM7x cells binding to each host cell, massive host cell death, and a host population crash. However, further passaging reveals that XH001n becomes less susceptible to TM7x over time and enters a long-term stable relationship similar to that of XH001. We show that this reduced susceptibility is driven by rapid host evolution that, in contrast to many forms of phage resistance, offers only partial protection. The result is a stalemate where infected hosts cannot shed their parasites; nevertheless, parasite load is sufficiently low that the host population persists. Finally, we show that TM7x can infect and form stable long-term relationships with other species in a single clade of , displaying a narrow host range. This system serves as a model to understand how parasitic bacteria with reduced genomes such as those of the Candidate Phyla Radiation have persisted with their hosts and ultimately expanded in their diversity.
四分之一的细菌多样性由一个具有缩小基因组的单一辐射组成,统称为候选门辐射。最近,我们共同分离出候选门辐射门萨卡里巴细菌门的一个超小型菌株 TM7x,与它的细菌宿主 s 菌株 XH001 一起从人类口腔中分离出来,并稳定地维持为共培养物。我们目前的工作表明,在共培养物中,TM7x 细胞通过感染种群的一部分来与宿主细胞建立长期寄生关系,这部分细胞保持存活,但细胞分裂受到严重抑制。相比之下,暴露于 TM7x 细胞的天真 s 分离株 XH001n 会导致大量 TM7x 细胞结合到每个宿主细胞上,宿主细胞大量死亡,宿主种群崩溃。然而,进一步传代表明,随着时间的推移,XH001n 对 TM7x 的敏感性降低,并进入类似于 XH001 的长期稳定关系。我们表明,这种降低的敏感性是由宿主的快速进化驱动的,与许多形式的噬菌体抗性不同,这种进化提供的只是部分保护。结果是一种僵局,感染的宿主无法摆脱寄生虫;然而,寄生虫的负荷足够低,宿主种群得以持续存在。最后,我们表明 TM7x 可以感染并与 单一种群中的其他物种形成稳定的长期关系,显示出狭窄的宿主范围。该系统可作为理解候选门辐射等具有缩小基因组的寄生细菌如何与宿主共存并最终扩大其多样性的模型。