# Domestication and characterization of TM7-the most elusive oral phylum

> **NIH NIH R01** · ADA FORSYTH INSTITUTE, INC. · 2021 · $413,015

## Abstract

Abstract
The overall goal of this application is to characterize newly discovered ultra-small parasitic bacteria that have
extremely reduced genomes and show increased abundance in gingivitis and periodontitis. In the previous
funding cycle, we successfully cultivated and sequenced TM7x, the first member of the uncultivated TM7
phylum from humans. Strain TM7x is unique among all bacteria, it has an ultrasmall size (200-300 nm) and
lives on the surface of a host bacterium, a relationship that had never been reported in the human microbiome
or in the Bacteria domain. With a highly-reduced genome, TM7x cannot synthesize any of its own amino acids,
vitamins or cell wall precursors and must parasitize other oral bacteria which impacts their growth. Of particular
note is that TM7 belongs to the Candidate Phyla Radiation (CPR), a recently discovered subdivision in the
domain Bacteria that comprises >26% of the known bacterial diversity with an estimated 70 uncultivated Phyla
with reduced genomes. To date, TM7x is still the only reported cultivated representative of the entire CPR,
putting our team in a unique position to make significant advancements in the field and facilitate fundamental
discoveries on these ultra-small human associated bacteria, as well as the CPR group as a whole.
Our preliminary data revealed that the relationship of TM7x and its bacterial host, an oral Actinomyces
odontolyticus strain XH001 is a highly-regulated symbiotic interaction in which TM7x displays both symbiotic
phase (co-existing with host) and virulent parasitic phase (inducing host cell death). This intriguing relationship
is similar to the one observed for temperate bacteriophages and their hosts where phages are capable of
switching between lysogenic and lytic cycle, and entails physiological and ecological consequences. In this
application, we aim to achieve the following two goals. 1) To identify the molecular components and regulatory
pathways governing the relationship between TM7x and its host; 2) To investigate the range of bacteria that
TM7x interacts with. In particular, the mechanism of host killing encoded within a bacterial parasite with a
reduced genome is both fundamentally novel and clinically relevant. The ability to infect and kill multiple
bacterial hosts may allow TM7x to influence the oral community dynamics and structure, thus modulating
community and impacting microbiome during health and diseases.
The success of the study would greatly advance the developing research field of these ultra-small bacteria,
expand our knowledge on this novel microbial symbiosis found in humans, as well as the potential impact of
CPR organisms on oral microbiome ecology.

## Key facts

- **NIH application ID:** 10115528
- **Project number:** 5R01DE023810-09
- **Recipient organization:** ADA FORSYTH INSTITUTE, INC.
- **Principal Investigator:** Xuesong He
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $413,015
- **Award type:** 5
- **Project period:** 2014-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115528

## Citation

> US National Institutes of Health, RePORTER application 10115528, Domestication and characterization of TM7-the most elusive oral phylum (5R01DE023810-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115528. Licensed CC0.

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