The human microbiome project has provided a comprehensive inventory of the microorganisms associated with the human body. The next challenge is to understand their role in human health and disease which requires cultivation of the species of interest. Relevant to this application, more than half of the oral microorganisms are categorized as uncultivated phylotypes including many associated with oral microbial pathogenesis. Among them, members of the candidate division TM7 phylum are the most enigmatic bacterial group in the oral cavity. Despite their ubiquitous occurrence in human body sites and other environments, no TM7 representative has been cultivated as pure culture. As a phylum containing suspected pathogens associated with inflammatory mucosal diseases, particularly periodontitis, cultivation of TM7 and the ability to investigate their pathogenic features has become like a "Holy Grail" in microbiology. Using a novel medium and enrichment techniques, we were able to reduce TM7-containing cultures from a complex community to dual-species co-cultures containing the disease associated TM7 phylotype (TM7x) together with Atopobium parvulum or Veillonella atypica as partner strain. We hypothesize that the growth of TM7x requires specific partner species and that understanding their relationship may be the key for isolating pure culture of TM7x. Furthermore, the present semi-pure cultures of TM7x and the possible pure TM7x cultures obtained through this study will enable our ability to study genomics, interactomics and the pathogenic potential of TM7x. This application aims to test our hypothesis and achieve these goals through detailed molecular analyses of the relationship between TM7x and its partner species, improving the medium for cultivating pure TM7x, as well as exploring its pathogenic potential. The immediate impact of the study is the discovery of cultivation conditions for TM7x and the associated biological/physiological functions. The long-term significance of the study is the creation of a new pathway for cultivation of many other yet-to-be cultured potentially pathogenic species.

Public Health Relevance

Many of the harmful bacteria that live in our mouth cannot yet be grown in the laboratory and researchers can therefore not study how they cause disease. Our research is focused on finding new conditions to grow these bacteria in the test tube by studying their behavior when they grow in the presence of other bacteria that they need. Once we understand how to grow these bacteria in the laboratory, we can do experiments to investigate their role in our health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE023810-01
Application #
8612839
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2014-04-01
Project End
2018-12-31
Budget Start
2014-04-01
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$432,319
Indirect Cost
$94,787
Name
University of California Los Angeles
Department
Dentistry
Type
Schools of Dentistry
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
To, Thao T; Liu, Quanhui; Watling, Michael et al. (2016) Draft Genome Sequence of Low-Passage Clinical Isolate Porphyromonas gingivalis MP4-504. Genome Announc 4:
Edlund, Anna; Liu, Quanhui; Watling, Michael et al. (2016) High-Quality Draft Genome Sequence of Low-pH-Active Veillonella parvula Strain SHI-1, Isolated from Human Saliva within an In Vitro Oral Biofilm Model. Genome Announc 4:
Bor, Batbileg; Cen, Lujia; Agnello, Melissa et al. (2016) Morphological and physiological changes induced by contact-dependent interaction between Candida albicans and Fusobacterium nucleatum. Sci Rep 6:27956
Bor, Batbileg; Poweleit, Nicole; Bois, Justin S et al. (2016) Phenotypic and Physiological Characterization of the Epibiotic Interaction Between TM7x and Its Basibiont Actinomyces. Microb Ecol 71:243-55
McLean, Jeffrey S; Liu, Quanhui; Bor, Batbileg et al. (2016) Draft Genome Sequence of Actinomyces odontolyticus subsp. actinosynbacter Strain XH001, the Basibiont of an Oral TM7 Epibiont. Genome Announc 4:
He, Xuesong; McLean, Jeffrey S; Edlund, Anna et al. (2015) Cultivation of a human-associated TM7 phylotype reveals a reduced genome and epibiotic parasitic lifestyle. Proc Natl Acad Sci U S A 112:244-9
Wu, T; Cen, L; Kaplan, C et al. (2015) Cellular Components Mediating Coadherence of Candida albicans and Fusobacterium nucleatum. J Dent Res 94:1432-8
Guo, Lihong; McLean, Jeffrey S; Lux, Renate et al. (2015) The well-coordinated linkage between acidogenicity and aciduricity via insoluble glucans on the surface of Streptococcus mutans. Sci Rep 5:18015
McLean, Jeffrey S; Liu, Quanhui; Thompson, John et al. (2015) Draft Genome Sequence of "Candidatus Bacteroides periocalifornicus," a New Member of the Bacteriodetes Phylum Found within the Oral Microbiome of Periodontitis Patients. Genome Announc 3:
Guo, Lihong; McLean, Jeffrey S; Yang, Youngik et al. (2015) Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology. Proc Natl Acad Sci U S A 112:7569-74

Showing the most recent 10 out of 11 publications