Research looking at bacteria that live on or in us and are unculturable, that may be behind some diseases, and that some researchers call "microbial dark matter". From Red Orbit - Your Universe Online:
Microbiologists cultivate “microbial dark matter”
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.
From the American Microbiome Institute regarding the same research:
Strange, parasitic microbiome bacteria may be responsible for inflammatory diseases
There are many bugs in the microbiome that cannot be cultivated, and thus are incredibly difficult to study using normal culturing techniques. We only know about these bugs through DNA sequencing, and it often difficult to draw any substantial conclusions from this information. One such group of bugs that is highly abundant in the microbiome is the bacterial phylum TM7.
TM7 has been associated with numerous inflammatory diseases, like vaginosis, inflammatory bowel diseases and periodontitis, and DNA analysis shows that this bug has the ability to create many toxins. Studying this bug could lead to breakthroughs in microbiome diseases, but until now it was unculturable. Recently though, a team of scientists from around the United States were able to cultivate these bacteria and in doing so learned what makes this bacteria so unique, and possibly so pathogenic.
The team aimed their investigation at the oral microbiome, because TM7 is abundant in the mouth and highly associated with periodontitis. They took samples of spit and realized that TM7 only could grow when another bacteria, Actinomyces odontolyticus, was present. When they cultured these bacteria together in a saliva-like media they realized that the TM7 was physically attached to the surface of A. odontolyticus. Through further experimentation they learned that TM7 could never grow on its own, and needed A. odontolyticus to replicate. Furthermore, TM7 is parasitic, and kills A. odontolyticus when they are starved.
The researchers then investigated the pathogenicity of TM7. They learned that TM7 can evade detection by the immune system for itself and A. odontolyticus. They also discovered that the particular strain of TM7 they were studying was antibiotic resistant. Furthermore, sequencing of the TM7 showed the strain had amongst the smallest genomes ever discovered, and relies on the A. odontolyticus for production of many essential molecules, like amino acids. However, TM7’s small genome is very dense in the production of virulent molecules and toxins, perhaps necessary for its parasitic nature, which could also affect its human host.
This study raises many interesting points about pathogens in the microbiome. DNA sequencing is a great start to defining the microbiome, but often times culture, or in this case co-culture is necessary to drill down into the true virulence of bacteria. For instance, prior to this study A. odontolyticus was considered to be associated with many inflammatory diseases, but these researchers showed that it is likely TM7, not A. odontolyticus that is the true culprit. Alas, the complexity of the microbiome often times reveals many more questions than answers.