“The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug, make them resistant,” said Alexander Fleming, speaking in his Nobel Prize acceptance speech in 1945.

As predicted by the man who discovered the first antibiotic, antibiotic resistance is finally upon us. With an increase in access to drugs and medicine, the common man has started to take antibiotics for less and less serious reasons and ‘’underdose himself’’ by not finishing the complete course of antibiotics.

More and more resistant strains of bacteria have started developing. In 2016, a woman in Nevada died from a bacterial infection caused Klebsiella pneumoniae that was resistant to all available antibiotics. Bacterial resistance it is growing at a worryingly fast rate worldwide, and thus has become a top priority for WHO. It has been estimated that approximately 10 million people will die every year due to antibiotic resistance and it has become increasingly important that we find new interventions to stop this.

The answer to this may have been right in front of us this whole time. What is it, you may ask? Astonishing as it may sound but we can use viruses to kill bacteria. Bacteriophages, or phages for short, are viruses that specifically attack and kill bacteria. The name itself mean ‘bacteria eater’. This form of therapy was originally founded in the 1900s; however, the discovery and mass-production of antibiotics lead to this therapy being left behind.

 How does the therapy work?

A ‘cocktail’ of 5-6 different bacteriophages are injected into the patient’s body. As the phages travel through the bloodstream, they quickly recognise and land on the bacteria. The tail fibres of the virus attach with the wall of the bacterial cells and it punctures through the bacteria’s walls with a ‘spike or pin’ sort of structure. The phage then squeezes its tail and injects its genetic material from its (capsid) head, which flows through its tail.

The Genetic material allows the virus to take over the cell and ‘’forces’’ it to manufacture viral proteins that assemble to form new bacteriophages. More and more bacteriophages are made until the point that the bacterium is filled up with new phages. Finally, all the phages produce endolysin, an enzyme that causes the cell to burst (i.e. causes lysis of the cell) releasing more phages into the bloodstream that attack all the other bacteria.

Why is it so Effective?

The phages are highly specialized bacteria which means they only attack specific bacterial cell. Human Cells are completely immune to them! In addition to that, they kill only the bad specific bacterial, unlike the antibiotics that could even the good bacteria in e.g. your intestines. What if bacteria become resistant to these phages? They can’t! Their greatest strength lies in their ability to evolve with their host, therefore circumventing bacterial resistance. Even if the bacteria did manage to develop some sort of resistance, it would mean that it would have to lose its resistance to antibiotics! Using both antibiotic therapy and phage therapy could mean that we can combat any bacterial infection.

The Problems

On paper, bacteriophage therapy appears to be a highly efficient alternative to current antibiotics. However, there are disadvantages associated with its global implementation. First, there is a requirement to convince a generally sceptical public, as many are unsure of what viruses are, how they could work as a therapy, and how they differ from bacteria.

Next, to produce phages, scientists must grow a large quantity of dangerous bacteria that is the natural host of the phage and one they would want to kill. The bacteria is then infected with the phages, and the phages in turn reproduce and kill all the bacteria. It becomes difficult to isolate the phages from the dead bacteria as if any dead bacteria got into the bloodstream it could cause the patient to go into Sepsis.

Finally, there is concern about its safety and efficacy as most countries abandoned phage therapy many decades ago, and there is little data about these topics available; which is why e.g. the FDA hasn’t fully approved of it yet.

In conclusion, although there are many problems with this new ‘experimental treatment’ it seems to a very promising field to explore in the future and help us get closer to eradicating disease. The treatment is slowly become more accepted with the FDA approving ListshieldTM, a food additive containing phages, that kills Listeria monocytogenes, one of the most virulent foodborne pathogens and one cause of meningitis.

In the near future, as antibiotics lose their effectiveness, we may begin to use phage therapy as our first line of defence.

Pratham Upadhyay

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