Diverse Ultra-small Bacterial Parasites in the Human Oral Cavity

Objectives: Having cultured the only member of the Candidate Phyla Radiation (CPR) to date, TM7x, we sought to further our investigation of the Saccharibacteria phylum, also known as TM7, by using public metagenomic and 16S data in order to determine the prevalence and diversity of this novel group of bacteria in mammals.
Methods: We systematically captured the spectrum of known diversity within the Saccharibacteria phylum by reconstructing novel Class level genomes belonging to G3, G5, and G6 as well as additional oral G1 genomes through cultivation enrichment and/or metagenomic binning.
Results: Capturing new oral genomes revealed the Saccharibacteria phylum contains genomically diverse groups (G1-G6) across human body sites as well as other mammalian hosts. Our work indicates the Saccharibacteria phyla may be more prevalent in humans than initially thought, as much as 84%, and even increase in abundance within some disease states. All novel genomes we have assembled, analyzed, and named seem to share similar characteristics to TM7x in their reduced cell and genome size as well as the lack of ability to carry out de novo biosynthesis of many essential compounds. Interestingly, diversity within the G1 group had considerably high synteny between both oral and environmental genomes, yet GC content and amino acid identity (AAI) between the different Saccharibacteria groups was highly variable, with the nearest clades only sharing 50% AAI – resulting in an obscure evolutionary past.
Conclusions: The Saccharibacteria phylum is more diverse and prevalent than previously thought. Although the evolutionary relationship between humans, mammals, and the environment within this phylum remains unresolved, this work has now provided the reference genomes necessary to better investigate these elusive bacteria, which is critical in order to understand the evolution and unique survival characteristics of these nano-sized bacteria and to determine the extent in which they may play a role in human health.