Friend or Foe? Six Degrees of Separation, Bacterial Style

Bifidobacteria is the name of the bacteria that are major inhabitants of the gastrointestinal tract of humans. These are the “good bacteria.”  Many bifidobacterial species are believed to contribute to nutrition, development and activity of a strong immune system. These beneficial health effects have driven commercial use of bifidobacteria as live components of many functional foods and can be found in natural food supplement stores.

However, bifidobacteria have also been isolated from the human mouth, where their presence is linked to tooth decay, the “bad bacteria.”  This species is capable of acid production in the mouth to produce a final pH below pH 4.2, sufficient to cause dissolve the calcium out of teeth.

Scientists from China, Italy, France, the UK, Ireland, and Canada (but not the USA!) have determined the complete sequence of the bad guys, all  2,636,368 letters of the genetic code, and have now compared it to prior good guy sequences to answer the question:

How many genetic adaptions does it take to go from being man’s best friend (feather-weight division!) to being responsible for dental  caries, which is one of the most common chronic diseases, remaining untreated in many underdeveloped countries where tooth pain is often alleviated only by the loss or extraction of the affected tooth?

Hint: the term six degrees of freedom refers to the idea that each person is only six steps from every other person on the planet earth. As an aside, the math behind it helps explain the growth rate of popular website visits fairly accurately.  But back to tooth decay.

You guessed it; if Mr. Wonderful acquires just six key genes, out of 2143 protein genes,  it becomes Mr. Tooth Decay!

And the genes acquired are the enzymes that take sugars in the diet and use them for fuel, at the same time making enough acid to dissolve teeth!

After the researchers made these discoveries, they decided to have some fun with the bug as well.  They grew them in the presence of dilute mouth wash, you know, the one you 'love to hate' and looked at which genes were changed.  This exposure turned on 112 genes that helped them break the mouth wash ingredient's molecules in two as well as spit them out of the cell (the multidrug transporter mdrB to be specific).  

What do you do with this information? Well developing a vaccine against these six proteins could lead to a pretty neat picture: eat all the candy you want as a kid and never have to visit the dentist!  And you shouldn't disturb the Good Guys in the GI tract since they don't make those proteins anyway.

Note: science and drug development is never this simple.  At last count there were more than 300 different species of bacteria isolated from tooth cavities. So before you can rid the world of the dental drill we need some more basic science.  I thought the map of the genome was kind of pretty.

Citation:

Citation: Ventura M, Turroni F, Zomer A, Foroni E, Giubellini V, et al. (2009) The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity. PLoS Genet 5(12): e1000785. doi:10.1371/journal.pgen.1000785.

The new cigarette labeling: "A Mutation in Every Pack"

Using the latest gene sequencing technique, scientists for the first time have the complete sequence of lung cancer- all 23, 000 mutations!!

Now with only 23,000 protein genes that works out to one mutation per protein.  When I first heard this I thought, no way, where are the DNA repair systems we heard about in school.  While the authors saw lots of evidence of repair, it just couldn't keep up.  Imagine how many mutations there would have been without good repair.

In fact they found a new system of repair that seemed to work in the 'more important' areas of the DNA than in the non-important areas.

Now for the chemists.  When you take the 60 or so chemicals found in tobacco smoke and treat DNA in a test tube you break or modify specific bonds in the DNA in a 'signature' reaction that always is the same and therefore can be identified with each of the 60 chemicals.  So what kinds of signature reactions in the lung cancer DNA? You guessed it. The 'signature' for tobacco damage.  Cause and effect has been taken to the level of the chemical bond.

But just to be clear. This was a test of normal and cancerous DNA from the same person.  The next person they study in this way is likely to have the same number of mutations but very few will be exactly in the same place.  After all, even with 23,000 mutations that is only one mutation for each 300,000 bases in the total DNA. So we are left with the unpleasant conclusion that every cancer is unique and that the Holy Grail of modern research, personalized medicine, is a cruel joke on the pharmaceutical industry and is too true- no two cancer patients have the same disease and therapy will have to be developed for a market of one person.  The Blockbuster drugs of the last century, defined as $1.0 B US in sales per year, will be a history lesson only.

Finally, the authors calculated that the mutation rate coupled with the smoking rate lead to the bizarre conclusion that you get one mutation for every 15 cigarettes.  So the Surgeon General can now put on the label of each pack:  "I have determined that this pack of cigarettes is going to cause a mutation in one of the cells of your lungs. Many are innocent but some will cause cancer. So the question you've got to ask yourself is,

"Do I feel lucky today?"

I thought these were interesting pictures- like looking up close at the fangs of a Cobra. This is the genetic picture of death as painted by lung cancer (top) and colon cancer (bottom).

Pubmed Reference

Atossa Genetics Forbes.com Interview

Atossa Genetics Forbes.com Interview video link

I had the opportunity of meeting Maureen Farrell (Maureen's Twitter Site) of Forbes.com in New York city recently.  This interview appeared on the Forbes.com Video Network program Breakout!  I am excited about the prospect that adding this breast cancer screening test as an adjunct to mammography will improve the sensitivity of detecting early breast cancer.

The QuayBlog Introduction

This is the first posting for the QuayBlog, a random account of activities in the world of biotechnology, medical devices, and other healthcare advances. Since I am new to this format your patience is requested.