Vitamin B12 Could Be Our Shot At An Alternative To Antibiotics

With the help of killer molecules known as PNAs, it may be the key to stalling the growth of bacterial cells.
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The antibiotic resistance crisis continues with no end in sight. Even as public health authorities across the globe call for action, we have yet to slow the arrival of the post-antibiotic era. Should this unfortunate milestone be reached, even the most common bacterial infections could be life threatening.

In laboratories around the world, researchers are trying to find alternative ways to treat bacterial infections. Some progress has been made in the form of viruses, known as bacteriophages, and small proteins known as antimicrobial peptides. Yet their use is limited at present and may not be enough to deal with all types of bacteria.

Colour-enhanced scanning electron micrograph showing Salmonella typhimurium, red, invading cultured human cells.
Colour-enhanced scanning electron micrograph showing Salmonella typhimurium, red, invading cultured human cells.

One of the most effective means to deal with bacteria is to ensure they cannot grow. This approach blocks the bacteria from producing the proteins necessary to survive. It's known as antisense inhibition and as research has shown, it can be incredibly difficult for the bacterium to resist.

For the last two decades, the strategy for effective antisense inhibition has focused on a particular type of molecule known as a peptide nucleic acid, or PNA. As the name implies, it's a hybrid of a small protein, a peptide and a piece of genetic material, which is made from nucleic acids. The goal is to stop bacteria in their tracks before they can find a way to grow and multiply.

The mechanism behind antisense inhibition is fascinating. The PNAs enter the bacterial cell and bind to a piece of the genetic material such that it cannot be used. If the gene happens to be necessary for survival, the PNA eventually causes the bacterium to die. It's quick and effective with little chance for resistance.

Unfortunately, you won't find PNAs in drug stores. That's because researchers have had troubles getting the killer molecules into bacteria. Unlike antibiotics and antimicrobial peptides, PNAs need to be taken into the cell willingly. Convincing a bacterium to do so has been a significant hurdle.

They found they could use a molecule most bacteria welcome into the cell as a Trojan horse for PNAs.

Now thanks to a group of Polish researchers, an answer may be at hand. They found they could use a molecule most bacteria welcome into the cell as a Trojan horse for PNAs. The results reveal that the next realm of bacteria treatments may depend on something we all know and seek out in our own diets — vitamin B12.

Much like humans, many bacterial species are unable to make this essential molecule and must acquire it from the environment. These include pathogens such as Escherichia coli and Salmonella typhimurium. For the researchers, this need represented a potentially critical weakness.

Because this concept had never been explored before, the team did all of their experiments in the lab. The E. coli and S. typhimurium strains they used were designed such that they could produce a red glow under blue light. The group hoped to target these genes with PNAs. If they were successful, the cells would no longer glow. This would be a perfect visual method to determine if their experiments were working.

With the strains chosen, the team went about making a B12-PNA molecule to target the red-glowing gene. The group chemically linked up B12 to the PNA such that the bacteria wouldn't realize the vitamin had an unwanted attachment. It took a little bit of trial and error, but eventually they found the right configuration to convince the cells they were accepting a nutrient rather than a threat to their survival.

A molecular model of Vitamin B12, or cyanocobalamin.
A molecular model of Vitamin B12, or cyanocobalamin.

At this point, the experiments followed a simple path. The bacteria were allowed to grow normally and then were exposed to either the B12-PNA creation or another B12-PNA using random genetic sequences. After several hours, the group looked for that red glow in both bacterial groups.

Just as expected, the glow was reduced when proper B12-PNA was used. In comparison, the random PNA sequence did nothing. The test was a success and proved the usefulness of the molecule as a replacement for antibiotics at least in the lab environment.

For the authors, the use of B12 may be the key to improving the chances PNAs can be accepted into bacterial cells. Although they only tested two species, the team notes almost all pathogenic bacteria need B12 to survive and thus may also be treated using this method. While future experiments will take some time, there appears to be considerable promise for this new direction in dealing with bacterial infections.

In the meantime, while we await the development of B12-PNAs, as well as bacteriophages and antimicrobial peptides, we can help to slow the pace of antibiotic resistance now through some very simple actions. The most important is to be cautious about asking for an antibiotic without knowing an infection is bacterial in nature. If one is prescribed, make sure to take the full course to reduce the chances for resistance due to survivors. Finally, the purchase of meats from animals raised without antibiotics will pressure the industry to forgo their use of these drugs. Combined, these actions will help to preserve our antibiotic supply until effective alternatives are properly developed and approved.

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