This episode features Dr. Batbileg Bor of the ADA Forsyth Institute, a leading expert on the Candidate Phyla Radiation (CPR), focusing on the enigmatic oral bacteria known as Saccharibacteria (TM7). Traditionally labeled as "microbial dark matter" due to their recalcitrance to cultivation, TM7 members are ultrasmall, obligate epibionts that live on the surfaces of host bacteria, primarily Actinomyces and Schaalia species. Dr. Bor details the paradigm-shifting discovery that despite their correlation with inflammatory states like periodontitis, TM7 may actually serve a protective role by modulating the pathogenicity of their host bacteria.
The discussion covers the physiological impacts of TM7 on its hosts—including induced cell elongation, thickened cell walls, and altered metabolism—and the molecular machinery involved, specifically the deployment of two distinct Type IV pili (T4P). One, a 1.8nm thin pilus, is the narrowest recorded and is essential for host-tethering, while the other drives twitching motility. The conversation underscores a broader ecological view of the human mouth as a complex landscape of interbacterial "sociomicrobiology," where ultrasmall symbionts dictate the inflammatory outcomes of the entire community.
Sociomicrobiology and Symbiosis: Investigating Saccharibacteria in the Oral Microbiome
8:45 Microbial Dark Matter: Saccharibacteria (TM7) represent a significant portion of the "Candidate Phyla Radiation" (CPR), a major evolutionary lineage that accounts for approximately 25% to 50% of all microbial diversity. These organisms are characterized by ultrasmall cell sizes (200–300 nm) and highly reduced genomes (~700 genes).
14:06 Accidental Cultivation: The first oral TM7 (TM7x) was successfully cultured in 2014. The breakthrough occurred partly by accident when an anaerobic chamber failure revealed that these organisms thrive best in microaerophilic conditions (2% oxygen).
18:31 Obligate Epibiosis: TM7 are obligate parasites (or episymbionts) that cannot survive or replicate without physical attachment to a host bacterium, such as Schaalia odontolytica (XH001). They lack the metabolic pathways to synthesize essential amino acids, nucleotides, and lipids, sourcing these instead from their hosts.
24:29 Morphological Stress Response: Association with TM7 induces dramatic changes in the host's morphology. Host cells transform from short rods to elongated, branched (hyphal) structures. Cryo-ET imaging revealed that TM7 infection also results in host cell walls thickening from ~15 nm to over 40 nm.
31:40 Population Dynamics: Initial infection of a naive host by TM7 often results in a "growth-crash" where host numbers drop precipitously. However, the system eventually reaches a stable steady state where a subpopulation of host cells persists and evolves decreased susceptibility.
42:26 Specialized Extracellular Pili: TM7x deploys two visually and functionally distinct Type IV pili (T4P). The "thin" pilus (1.8 nm diameter) is non-retractile and serves as a long-range host-tethering factor. The "thick" pilus (3.2 nm) is essential for survival and drives twitching motility.
50:04 Paradigm Shift in Periodontitis: While TM7 levels increase in diseased periodontal pockets, mouse model studies indicate they may be "inflammophilic" rather than strictly pathogenic. In experiments, TM7/host-bacteria pairs induced significantly less bone loss than the host bacteria alone.
53:45 Pathogenicity Modulation: TM7 protects the mammalian host by downregulating virulence factors in the host bacteria, specifically inhibiting collagen-binding proteins and sialic acid metabolism (the nanE operon), effectively transitioning the host bacterium from a pathobiont to a commensal.
1:01:15 Complex Life Cycle: TM7 appears to have a dual-host cycle, utilizing both a human host (binding to gingival epithelial cells via TLR2 pathways) and a bacterial host for replication and horizontal transmission.