Dr Bas Dutilh’s crAss discoveres crAssphage Virus - How Bacteriophages can prevent Colorectal Cancer and attack other Bacteria

“Initially we didn’t give it any name, it was just called ‘the new virus'. Then I was like, Oh okay, maybe I can use this opportunity to advertise my computer tool. And basically that’s how it got the name crAssphage.”

Dr Bas Dutilh, a bioinformatician at Radboud University Medical Centre in the Netherlands explaining how crAssphage got its name

Turns out there’s a war going on in your stomach, which is a battlefield between Bacteroides Strain of Bacteria and crAssphage Virus.

It’s the bad Bacteria vs Bacteriophage, those Bacteria killing Viruses that I wrote about awhile back in my blog article entitled “Bacteriophage Therapy from former USSR State Georgia is a potential treatment against Super-bug Bacteria - Hansel and Gretel Witch Hunters Panacea to eradicate Bacterial infections”.

The Bacteriophage in this case is the crAssphage, a bacteriophage discovered by Dr Bas Dutilh, a bioinformatician at Radboud University Medical Centre in the Netherlands as explained in “A Common Virus Is Eating Your Gut Bacteria”, published 8/02/2014 @ 1:06PM by JV Chamary, Forbes. 

It gets its rather odd name from the fact that he developed a computer program called crAss (short for 'Cross Assembly') that reassembles the Genetic material harvested from feces into separate genomes and Genes associated with a particular organism, as fecal Bacteria genetic information will be all mixed up on exit from the anus.

His work, which was published in the Journal of Nature in the article “A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes” published 24 July 2014, Nature is part of a collaborative decade long effort by geneticists to determine the Genetic sequence of Bacteria, viruses and other organisms living in your Stomach, Small Intestine and Large Intestine.

This US$170 million project, called the Human Microbiome Project, involves extracting the Bacteria from some 242 adults across the world at five (5) locations on their bodies:

1.      Mouth

2.      Nose

3.      Skin

4.      Urogenital Tracts i.e. urine

5.      Gastrointestinal tracts i.e. Fecal matter

This sample is then killed via pasteurization, most likely via vacuum pyrolysis. Using traditional Genome sequencing techniques combined with advanced algorithms such as crAss, the different protein and DNA fragments are reassembled into Genes. These Genes are then grouped into Genomes and thus the Genome Sequence is determined for each Bacteria and virus in the stomach. It was using this method that Dr Bas Dutilh made his discovery.

But how does Dr Bas Dutilh computational tool crAss work? And what's so important about the crAssphage Virus anyway?

Dr Bas Dutilh’s crAss at work - crAssphage Virus saves you from Colorectal Cancer

First, a quick primer on how Dr Bas Dutilh computational tool crAss works!

In Dr Bas Dutilh study, his team worked with researchers at San Diego State University who assisted with the analysis of the fecal matter from 12 persons.

Since the DNA material is part of a massive mixture of genetic material known as a metagenome, the program looks for common pieces across the various samples, like similar fitting pieces in a mixed up set of Lego pieces. If the same Genetic material turns up in different metagenome samples from the 12, then it's safe to say they're part of the same organism.

Confirmation of what eventually became known as crAssphage was done via further DNA analysis on one of the twelve samples.

Based on his work, the crAssphage virus is now fully sequenced and is known to have a genome with 80 Genes and a total of 97,000 Base pairs. Even more interesting is that the proteins that these based pairs encode for are proteins that allow the crAssphage to take over a Bacteria but also specifies which Bacteria it attacks, in this case the of Bacteroides Strain of Bacteria.

Most of the Bacteroides Strain of Bacteria are good and bad Bacteria as described in “Bacteroides: the Good, the Bad, and the Nitty-Gritty” by Hannah M. Wexler, Clinical Microbiology Review.

The Bacteroides Strain of Bacteria and constitute some 50% of the population of Bacteria in your stomach as explained in the study “Structure, function and diversity of the healthy human microbiome”, published 14 June 2012, Nature. They are a part of the Probiotics that help with healthy digestion of certain types of animal proteins, very leafy and starchy foods and the production of roughage for the easy passage of stool.

Because they are often killed off by certain antibiotics such as in the case of the treatment of a Clostridium difficile infection, enemas had to be done to replace these good Bacteria in what's effectively a fecal transplant as described in my blog article entitled “University of Calgary develops Fecal Transplant to repopulate the Large Intestine after a Clostridium difficile treatment - How to cure diarrhoea, cramping and bloating after eating infected food”.

crAssphage hates Bacteroides fragilis - GM love-hate relationship against other Bacteria

The crAssphage bacteriophage specifically attacks the Bacteroides fragilis, a bacterium with a toxic coating that is suspected of causing Colorectal Cancer as stated in “Enterotoxigenic Bacteroides fragilis: a Rogue among Symbiotes” by Cynthia L. Sears, Clinical Microbiology Reviews.

By attacking this particular bad member of the Bacteroides Strain of Bacteria, it's helping to keep Colorectal Cancer at bay. Now that Dr Bas Dutilh has identified the genome of this particular crAssphage bacteriophage, it can also be cultured or extracted from healthy donors and possibly used in enemas or fecal transplant to treat early stages of Colorectal Cancer.

Additionally, the researchers found that this beneficial bacteriophage was in 74% of the 466 fecal metagenomes from across the world, particularly in US, Europe and South Korea participants in the study. This suggests, even without the completion of the US$170 million Human Microbiome Project, that the crAssphage bacteriophage is a common organism living in the stomachs of many humans worldwide. 

In fact, the abundance of crAssphage Virus and Bacteroides fragilis that it targets became obvious when the crAssphage DNA was compared against 151 metagenomes in the Human Microbiome Project. They found that in their database of 3000 bacterial genomes, the correlation between bacterium DNA that matched what the crAssphage Virus DNA that determined which bacterium it was targeting, which is called the CRISPR Sequence, indicated that the Bacteroides family of Bacteria were the top of its hitlist!

However, despair not, as GM (Genetic Modification) comes to the rescue!

This crAssphage bacteriophage has a bright future as a delivery mechanism for vitamins and minerals not to mention being genetically modified to also attack other Bacteria such as Anthrax, Escherichia Coli, Cholera, Malaria or other bacterium as described in my blog article entitled “Bacteriophage Therapy from former USSR State Georgia is a potential treatment against Super-bug Bacteria - Hansel and Gretel Witch Hunters Panacea to eradicate Bacterial infections”.

So much for pharmaceutical usages, as Big Pharmaceutical companies may not like the idea of a virus that could potentially cure a lot of illnesses caused by Bacteria that's so easily harvested and administered. Still a cure for so many bacterial infections makes Bacteriophages the number probiotic alternative to antibiotics that are increasingly resistant to drugs.