Intricate Interactions Between an Oral Bacterium, Its Episymbiont, and Bacteriophages
Objectives: Technological advances allow a more holistic approach when studying oral microbiome: to expand from conventional bacteria-, and fungi-oriented study to other under-investigated microbial types, such as bacteriophages and recently identified nano-sized Candidate Phyla Radiation (CPR) organisms, including Saccharibacteria (formerly TM7). Here, we established a multi-party microbial system, which comprises an oral Schaalia odontolytica strain XH001, a Saccharibacteria Nanosynbacter lyticus strain TM7x which is the first culture representative of CPR bacterium with a highly reduced genome, a prophage and a lytic phage. TM7x lives on the surface of its host bacterium XH001, forming a unique episymbiotic relationship. The episymbiotic association significantly affects the behavior of an XH001-encoded prophage (named xhp1), and modulates the interaction between XH001 and an oral lytic phage (named LC001). Our long-term goal is to use this system to understand the biological, ecological and pathogenic impact of the interactions of phylogenetically distant but ecologically intimate oral microorganisms. Methods: The main techniques employed include: Lipidspotâ staining, Raman Spectroscopy, Bacterial-phage co-evolution assay, bacterial genetics, RNAseq. Results: We provided intriguing findings, many of which have not been reported in human-associated microbiome studies: 1) TM7x association triggers lipid droplet production in XH001, and this is mediated through XH001-encoded prophage xhp1, leading to enhanced survival of XH001 under stress conditions; 2) The association of TM7x protects XH001 from infection by oral lytic phage LC001, promoting long-term coexistence of bacterium XH001 and its lytic phage within the oral cavity, which is of ecological significance; 3) XH001-encoded prophage xhp1 is prone to activation when XH001 forms episymbiosis with TM7x. The released xhp1 induces antiviral immunity and inhibits antibacterial response in the mammalian host. Conclusions: Phages engage in intricate interaction with bacterial residents of the oral microbial community and exert a far-reaching influence on bacterial physiology, microbial ecology, and pathogenesis.