Saccharibacteria (TM7) in the Human Oral Microbiome

Abstract

Bacteria from the Saccharibacteria phylum (formerly known as TM7) are ubiquitous members of the human oral microbiome and are part of the Candidate Phyla Radiation. Recent studies have revealed remarkable 16S rRNA diversity in environmental and mammalian host-associated members across this phylum, and their association with oral mucosal infectious diseases has been reported. However, due to their recalcitrance to conventional cultivation, TM7's physiology, lifestyle, and role in health and diseases remain elusive. The recent cultivation and characterization of Nanosynbacter lyticus type strain TM7x (HMT_952)-the first Saccharibacteria strain coisolated as an ultrasmall obligate parasite with its bacterial host from the human oral cavity-provide a rare glimpse into the novel symbiotic lifestyle of these enigmatic human-associated bacteria. TM7x is unique among all bacteria: it has an ultrasmall size and lives on the surface of its host bacterium. With a highly reduced genome, it lacks the ability to synthesize any of its own amino acids, vitamins, or cell wall precursors and must parasitize other oral bacteria. TM7x displays a highly dynamic interaction with its bacterial hosts, as reflected by the reciprocal morphologic and physiologic changes in both partners. Furthermore, depending on environmental conditions, TM7x can exhibit virulent killing of its host bacterium. Thus, Saccharibacteria potentially affect oral microbial ecology by modulating the oral microbiome structure hierarchy and functionality through affecting the bacterial host's physiology, inhibiting the host's growth dynamics, or affecting the relative abundance of the host via direct killing. At this time, several other uncharacterized members of this phylum have been detected in various human body sites at high prevalence. In the oral cavity alone, at least 6 distinct groups vary widely in relative abundance across anatomic sites. Here, we review the current knowledge on the diversity and unique biology of this recently uncovered group of ultrasmall bacteria.

Keywords: candidate phyla radiation; epiparasite; interspecies interaction; periodontitis; symbiont; ultra-small bacteria.

Figure 1.

Saccharibacteria (TM7) biogeography in the oral cavity. With the accumulated availability of 16S rRNA gene sequences in databases, the phylogenetic diversity of the phylum results in at least 6 major taxonomic groups, which are detected at various levels in the oral cavity. Pie charts displaying the percentage distribution of the different groups within the phylum across oral cavity sites were derived from a reanalysis of the Human Microbiome Project data (https://hmpdacc.org/) with recently established reference sequences from the different groups.

Figure 2.

Genome scale metabolic maps of the XH001 and TM7x interaction. Curated, genome scale metabolic models of XH001 and TM7x derived from collaboration with the Biocyc team, which is publically available (https://biocyc.org/). There is a major contrast in the predicted functions for each of these bacteria. Actinomyces odontolyticus XH001 has 123 pathways and 774 reactions and 501 predicted enzymes. The reduced genome parasite TM7x is auxotrophic for all essential amino acids and in comparison has only 20 pathways and 151 reactions with 101 predicted enzymes. XH001: Actinomyces odontolyticus strain XH00; TM7x: Nanosynbacter lyticus type strain TM7x.

Figure 3.

Flux balance analysis of the XH001 and TM7x interaction. Flux balance analysis using the Seed Model (http://modelseed.org/) enables a cursory prediction of the possible metabolic interaction between the two species in minimal media with glucose as the carbon source. Lactate under these conditions is the predicted substrate for TM7x metabolism. Colored nodes represent compounds and lines with numbers represent the predicted flux of metabolites. XH001: Actinomyces odontolyticus strain XH001; TM7x: Nanosynbacter lyticus type strain TM7x.

Figure 4.

TM7x represents the first CPR bacteria cocultivated with its host. (a) Current view of the tree of life highlights TM7 and CPR (tree inferred from concatenated ribosomal gene data set provided by Hug et al. 2016). (b) Fluorescence in situ hybridization image shows the epiparasitic relationship between TM7x and its bacterial host XH001. (c) TM7x/XH001 provides a better understanding of bacterial epiparasitic interaction: (1) a detailed mechanistic understanding of the dynamic parasitic interaction between TM7x and its host bacterium XH001; (2) the host selection and host range of TM7x; (3) the impact of interaction on bacterial physiology; and (4) pathogenic potential. CPR, Candidate Phyla Radiation. XH001: Actinomyces odontolyticus strain XH00; TM7x: Nanosynbacter lyticus type strain TM7x.