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Feb 18, 2014

Genome of Harmless Oral Microbe Sheds Light on Its Gum-Destroying Cousins

  • Many oral microbes, whether harmless or pathogenic, frustrate scientists because they refuse to grow in the laboratory. Such microbes, which include more than 60% of bacteria in the human mouth, have even been referred to as “biological dark matter.” Though these obscure species have never been cultivated, they are known to exist, but only because of DNA sequencing, which yields insights even if only individual cells, directly harvested from human hosts, are available.

    While it is possible to sequence the genome of a pathogenic species—such as Tannerella forsythia, which is linked to periodontitis—the hard-won genetic information may not seem especially meaningful. That is, it may not be clear which genes contribute to disease and which are relatively innocuous. That’s where comparative genomics comes in. By comparing the genome of T. forsythia to the genome of a closely related but harmless microbe, one may identify genes that occur only in the harmful relative. Such genes would be suitable targets for further study.

    By taking advantage of comparative genomics, scientists at Ohio State University and Oak Ridge National Laboratory have identified several genes that appear to account for the pathogenic potential of T. forsythia. They published their findings in an article published February 14 in PLOS ONE, in an article entitled “Single Cell Genomics of Uncultured, Health-Associated Tannerella BU063 (Oral Taxon 286) and Comparison to the Closely Related Pathogen Tannerella forsythia.”

    As the title indicates, the scientists compared T. forsythia with BU063, which is the closest relative to T. forsythia, but does not cause disease itself. They used single-cell genomics to isolate 12 individual BU063 cells by flow cytometry, and then the scientists amplified and sequenced the cells’ genomes: “Comparative analyses of the assembled genomic scaffolds and their gene contents allowed us to study the diversity of this taxon within the oral community of a single human donor that provided the sample. Eight different BU063 genotypes were represented.”

    The scientists reported that the genome of BU063 is, as expected, more similar to T. forsythia than any other known genome. However, they also found significant differences, including a 44% difference in gene content, changes in metabolic pathways, loss of synteny, and an 8–9% difference in GC content.

    Most importantly, the scientists noticed that several identified virulence genes of T. forsythia are not found in BU063 including karilysin, prtH, and bspA. Reflecting on the significance of this finding, the authors of the PLOS ONE article wrote: “The absence of these genes may explain the lack of periodontal pathogenesis by this species and provides a new foundation to further understand the genome evolution and mechanisms of bacterial-host interaction in closely related oral microbes with different pathogenicity potential.”

    The scientists also highlighted the diversity of species they found. “We expect people to have 150 to 200 species of bacteria in their mouths, but they may have all these layers underneath of 20 little variants—at least it’s a possibility based on this organism,” said Clifford Beall, Ph.D., research assistant professor of oral biology at Ohio State University and lead author of the study. “This may go to show that our microbiome is even more complicated than we’ve previously thought.”

    “There are a lot of different bacteria that are higher in periodontitis lesions, but we don’t see every one of those bacteria in every case of periodontitis,” added Dr. Beall. “So it’s hard to see a drug affecting one bacteria being very successful.”



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