Microbiologists cultivate “microbial dark matter”

Eric Hopton for redOrbit.com – Your Universe Online

Scientists from University of California Los Angeles (UCLA), J. Craig Venter Institute and the University of Washington have achieved a major breakthrough in the understanding of what they call “microbial dark matter.” These are the countless bacteria which inhabit our bodies and about which so little is known.

Amazingly, there are 10 times more bacterial cells in the body than other cells. But approximately half of those bacteria are almost impossible to replicate for scientific research. This has restricted our ability to understand their role in human biology and disease. This led to the term “microbial dark matter.” For a long time, biologists have thought that these “uncultivable bacteria” may be involved in the development of some serious and chronic diseases.

One particular bacteria group, Candidate Phylum TM7, has been an especially difficult challenge for researchers. Because it is so prevalent in people with periodontitis, an infection of the gums, TM7 has been implicated in causing inflammatory mucosal diseases. Decades of research into this connection proved fruitless. But now, in a major breakthrough, scientists at the UCLA School of Dentistry, the J. Craig Venter Institute and the University of Washington School of Dentistry believe they have cracked the problem.

Their work has revealed new information about the biological, ecological and medical importance of TM7 and its resistance to scientific study as well as its role in the progression of periodontitis and other diseases. The findings could lead to better understanding of other elusive bacteria.

The research results are published online in the December issue of the Proceedings of the National Academy of Sciences.

“I consider this the most exciting discovery in my 30-year career,” said Dr Wenyuan Shi, a UCLA professor of oral biology. “This study provides the roadmap for us to make every uncultivable bacterium cultivable.”

The researchers cultivated a specific type of TM7 called TM7x, a version of TM7 found in people’s mouths, and found the first known proof of a signalling interaction between the bacterium and an infectious agent called Actinomyces odontolyticus, or XH001, which causes mucosal inflammation.

“Once the team grew and sequenced TM7x, we could finally piece together how it makes a living in the human body,” said Dr. Jeff McLean, acting associate professor at the University of Washington School of Dentistry. “This may be the first example of a parasitic long-term attachment between two different bacteria — where one species lives on the surface of another species gaining essential nutrients and then decides to thank its host by attacking it.”

To prove that TM7x needs XH001 to grow and survive, the team attempted to mix isolated TM7x cells with other strains of bacteria. Only XH001 was able to establish a physical association with TM7x, which led researchers to believe that TM7x and XH001 might have evolved together during their establishment in the mouth.

The co-cultures collected in this study allowed researchers to examine, for the first time ever, the role which TM7x plays in chronic inflammation of the digestive tract, vaginal diseases and periodontitis.

“Uncultivable bacteria presents a fascinating ‘final frontier’ for dental microbiologists and are a high priority for the NIDCR research portfolio,” said Dr. R. Dwayne Lunsford, director of the National Institute of Dental and Craniofacial Research’s microbiology program. “This study provides a near-perfect case of how co-cultivation strategies and a thorough appreciation for interspecies signaling can facilitate the recovery of these elusive organisms. Although culture-independent studies can give us a snapshot of microbial diversity at a particular site, in order to truly understand physiology and virulence of an isolate, we must ultimately be able to grow and manipulate these bacteria in the lab.”

Scientists already knew that XH001 induces inflammation. But by infecting bone marrow cells with XH001 alone and then with the TM7x/XH001 co-culture, the researchers also found that inflammation was greatly reduced when TM7x was physically attached to XH001. This is the only known study that has provided evidence of this relationship between TM7 and XH001.

The researchers plan to further study the unique relationship between TM7X and XH001 and how they jointly cause mucosal disease. Their findings could have implications for potential treatment and therapeutics.

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