title: Cultivation of a human-associated TM7 phylotype reveals a reduced genome and epibiotic parasitic lifestyle.
abstract: The candidate phylum TM7 is globally distributed and often associated with human inflammatory mucosal diseases. Despite its prevalence, the TM7 phylum remains recalcitrant to cultivation, making it one of the most enigmatic phyla known. In this study, we cultivated a TM7 phylotype (TM7x) from the human oral cavity. This extremely small coccus (200-300 nm) has a distinctive lifestyle not previously observed in human-associated microbes. It is an obligate epibiont of an Actinomyces odontolyticus strain (XH001) yet also has a parasitic phase, thereby killing its host. This first completed genome (705 kb) for a human-associated TM7 phylotype revealed a complete lack of amino acid biosynthetic capacity. Comparative genomics analyses with uncultivated environmental TM7 assemblies show remarkable conserved gene synteny and only minimal gene loss/gain that may have occurred as TM7x adapted to conditions within the human host. Transcriptomic and metabolomic profiles provided the first indications, to our knowledge, that there is signaling interaction between TM7x and XH001. Furthermore, the induction of TNF-α production in macrophages by XH001 was repressed in the presence of TM7x, suggesting its potential immune suppression ability. Overall, our data provide intriguing insights into the uncultivability, pathogenicity, and unique lifestyle of this previously uncharacterized oral TM7 phylotype.
authors.affiliation: Section of Oral Biology, School of Dentistry, and.
authors.forename: Xuesong
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Periodontics, University of Washington, Seattle, WA 98195; Microbial and Environmental Genomics, J. Craig Venter Institute, San Diego, CA 92037; jsmclean@uw.edu wenyuan@ucla.edu.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: McLean
authors.affiliation: Section of Oral Biology, School of Dentistry, and Microbial and Environmental Genomics, J. Craig Venter Institute, San Diego, CA 92037;
authors.forename: Anna
authors.initials: A
authors.lastname: Edlund
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, San Diego, CA 92037;
authors.forename: Shibu
authors.initials: S
authors.lastname: Yooseph
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, San Diego, CA 92037;
authors.forename: Adam P
authors.initials: AP
authors.lastname: Hall
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;
authors.forename: Su-Yang
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Departments of Chemistry and Biochemistry and Pharmacology, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037;
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
authors.affiliation: Sirenas Marine Discovery, San Diego, CA 92121; and.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Esquenazi
authors.affiliation: Department of Microbiology, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Hunter
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Microbial and Environmental Genomics, J. Craig Venter Institute, San Diego, CA 92037;
authors.forename: Karen E
authors.initials: KE
authors.lastname: Nelson
authors.affiliation: Section of Oral Biology, School of Dentistry, and.
authors.forename: Renate
authors.initials: R
authors.lastname: Lux
authors.affiliation: Section of Oral Biology, School of Dentistry, and jsmclean@uw.edu wenyuan@ucla.edu.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
mesh_terms: D000190:Actinomyces; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics* / Q000254:growth & development* / Q000648:ultrastructure; D016680:Genome, Bacterial / Q000235:genetics*; D058507:Host Specificity; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D009055:Mouth / Q000382:microbiology; D010271:Parasites / Q000235:genetics*; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013559:Symbiosis; D026801:Synteny; D059467:Transcriptome / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: TM7; epibiont; human-associated; interspecies interaction; oral microbiome