AP Biology class blog for discussing current research in Biology

Tag: Bacteriophage

New anti-CRISPR Proteins Serving as Impediments to this Miraculous System.

CRISPR-Cas9 systems are bacterial immune systems that specifically target genomic sequences that in turn can enable the bacterium to fight off infecting phages. CRISPR stands for “clusters of regularly interspaced short palindromic repeats” and was  first demonstrated experimentally by Rodolphe Barrangou and a team of researchers at Danisco. Cas9 is a protein enzyme that is capable of cutting strands of DNA, associated with the specialized stretches of CRISPR DNA.

Diagram of the CRISPR prokaryotic antiviral defense mechanism.

Recently, a blockage to the systems was found by researchers which are essentially anti-CRISPR proteins. Before, research on these proteins had only showed that they can be used to reduce errors in certain genome editing. But now, according to Ruben Vazquez Uribe, Postdoc at the Novo Nordisk Foundation Center for Biosustainability (DTU), “We used a different approach that focused on anti-CRISPR functional activity rather than DNA sequence similarity. This approach enabled us to find anti-CRISPRs in bacteria that can’t necessarily be cultured or infected with phages. And the results are really exciting.” These genes were able to be discovered by DNA from four human faecal samples, two soil samples, one cow faecal sample and one pig faecal sample into a bacterial sample. In doing so, cells with anti-CRISPR genes would become resistant to an antibiotic while those without it would simply die. Further studies found 11 DNA fragments that stood against Cas9 and through this, researchers were ultimately able to identify 4 new anti-CRIPRS that “are present in bacteria found in multiple environments, for instance in bacteria living in insects’ gut, seawater and food,”  with each having different traits and properties.  “Today, most researchers using CRISPR-Cas9 have difficulties controlling the system and off-target activity. Therefore, anti-CRISPR systems are very important, because you want to be able to turn your system on and off to test the activity. Therefore, these new proteins could become very useful,” says Morten Sommer, Scientific Director and Professor at the Novo Nordisk Foundation Center for Biosustainability (DTU). Only time will tell what new, cool, and exciting discoveries will be made concerning this groundbreaking system! What else have you guys heard? Comment below!

Message Intercepted – Commence attack on bacteria!

Tevenphage – Photo credit to Wikimedia Commons

While experimenting, a group of scientists noticed that a A virus, VP882, was able to intercept and read the chemical messages between the bacteria to determine when was the best time to strike. Cholera bacteria communicate through molecular signals, a phenomenon known as quorum sensing, to check their population number.  The signal in question is called DPO.  VP 882, a subcategory of bacteria’s natural predator, the bacteriophage, waits for the bacteria to multiply and is able to check for the DPO.  Once there is enough bacteria, in the experiment’s case they observed cholera, the virus multiples and consumes the bacteria like an all-you-can-eat buffet. The scientists tested this by introducing DPO to a mixture of the virus and bacteria not producing DPO and found that that the bacteria was in fact being killed.

The great part about VP 882 is it’s shared characteristic with a plasmid, a ring of DNA that floats around the cell. This makes it easier to possibly genetically engineer the virus so that it will consume other types of bacteria. This entails it can be genetically altered to defeat other harmful bacterial infections, such as salmonella.

Ti plasmid – Photo credit to Wikimedia Commons

Current phage therapy is flawed because phages can only target a single type of bacteria, but infections can contain several types of different bacteria.  Patients then need a “cocktail” with a variety of phages, which is a difficult due to the amount of needed testing in order to get approved for usage.  With the engineering capability of using a single type of bacteria killer and the ability to turn it to kill bacteria, phage therapy might be able to advance leaps and bounds.

As humans’ storage of effective antibiotics depletes, time is ticking to find new ways to fight bacterial infections.  Are bacteriophages and bacteria-killing viruses like VP 882, the answers?

Virus VP882: Our Forgotten Spy to End our Bacteria Problem

The virus VP882, which had long ago sequenced in Taiwan as a part of a study of an outbreak of cholera, has now resurfaced and has the potential to make major waves in our addressing of the harmful bacteria. In recent years, biomagnification of harmful bacteria, in large part due to human waste, like Escherichia Coli and Vibrio Cholerae are having immediate and detrimental effects on our environment and in human health as well. For example, a significant amount of produce circulating in the United States has been contaminated with Escherichia Coli causing many to contract Shiga toxin-prducing E. coli infection (STEC) which, as according to the Centers for Diseases Control and Prevention (CDC), can causes “severe stomach cramps, diarrhea (often bloody), and vomiting”.

Our problem today is that the production of bacteria-specific responses to infection are difficult to produce and become costly as a result. Most of our anti-bacterials today target bacteria-made toxins, in order to restore affected G-Protein cell signaling function. Unfortunately, this treatment may negatively impact the integral human microbiome. An alternative way of countering bacterial infections is through use of phage therapy. This treatment is much more specific, bringing less harm to the host organism, and involves viruses to enter and reproduce in bacterial cells, eventually causing them to lyse, thus killing them. While objectively this process seems far superior than the current general treatment, too often the infective bacteria remains unknown, which as M.I.T. Professor Mark Mimee discusses in the Scientific American article on the VP882 virus, forces doctors to prescribe “a cocktails of different phages. But manufacturing cocktails and adhering to drug regulations is too expensive.” Then enters the VP882 virus.

The VP882 virus works just as most other bacteriophages: the virus uses bacteria as hosts for their reproduction, and cause them bacteria cells to lyse, after they have hijacked a given bacterium’s reproductive mechanisms. There are two things, though which make this virus special in the realm of bacteriophages. VP882 has the ability to sense bacterial cell communication and is a very simple structure, similar to a plasmid. This virus’s discovery can in part be credited to a coincidence. A student at Princeton, Justin Silpe, in his study of a molecule, DPO, which is integral in bacteria cell signaling, specifically quorum sensing, ran across this surprising virus which was sequenced in the presence of DPO. What he and his professor, Bonnie Bassler, found is that this virus, which was attacking cholera cells, was able to secretly calculate the optimal time to invade the bacteria (thus its many comparisons to a spy), by sensing a high quantity of DPO, which is a signal for when bacteria can begin their collective behavior, and possibly start a disease. What this means is that because of this ability to understand a bacteria’s quorum, they can most effectively counteract an infection.

In addition, upon further study, VP882 was found to be a very simple structure. This arguably the most important aspect of VP882. The virus is very similar to a plasmid, which can be easily modified and, thus accepted by a plethora of bacteria. This leads scientists like Bassler and Silpe to believe that VP882 can be modified to create an all-encompassing bacteriophage treatment, one which could be made cheaply and work far more effectively than general anti-bacterial treatments. Whether this is feasible still remains unknown, but in the time being, VP882 can be readily applied to neutralizing cholera in industrial wastewater without harming the natural microbiome, proving already the usefulness of this discovery.

Discharge Tube Releasing Cholera-filled Wastewater



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