Microbes are everywhere, on your phone, your notebook and even inside you. Every human has their own unique microbiome (a community of microbes) composed of bacteria, virus and other microorganisms. But good news for us; these microbes consists of good bacteria too that we have a pact with. We, as in humans, provide them with food and shelter, in turn they work for us and keep the bad microbes in check. These bacteria help us digest food, absorb nutrients from food that we cannot do so ourselves and even help our intestinal cells to grow.
But where there’s good there’s evil; our gut is also a perfect place for the evil Mojo JoJo’s’ (bad bacteria) to attack. The health deteriorating human lifestyle has led to the imbalance in gut microbiota, leading to favorable environment for the growth of bad bacteria that make us ill. These tiny monsters attack our cells, disrupt the normal functioning of the body and make us fall sick. These bacterial diseases have killed millions around the world. Recent research has showed that one of such bad bacteria called Fusobacterium Nucleatum plays a crucial role in the progression of Colorectal cancer (CRC), the 3rd deadliest cancer in the world causing thousands of deaths each year. This F. nucleatum not only supports the growth of CRC but also makes it resistant to drugs that kill cancer cells (chemotherapy).
About a 100 years ago we found a weapon to kill these monsters; Antibiotics. But we humans tend to misuse a power and that’s what we did. Antibiotics were so effective that we stopped thinking and used them as a weapon to cure diseases that were not that serious or didn’t demand use of antibiotics. We forgot that bacteria are also living things and that they evolve. They started to mutate and have now become immune to even the strongest antibiotics available for example colistin. These ‘Superbugs” are now predicted to kill more humans than cancer by 2050, because we will have no defense against them.
But there is a superhero that can save us from these deadly monsters, called Bacteriophage (in short called phages). Bacteriophages are small viruses that kill bacteria. There are more phages on earth than other microorganisms combined. They are everywhere but need a host to survive and reproduce. When a phage finds a victim, it injects its DNA into the bacteria which then incorporates itself into bacterial DNA, the headquarter issuing all commands, hijacks the bacterial machinery to produce multiple copies of itself. At the end the phages produce endolysin, a powerful super enzyme that punches a hole in bacteria and phages burst out of it, killing the bacteria in the process.
The most good thing about phages? They are very specialized and selective killers of bacteria, that is they only kill one specific type of bacteria or their close relatives, leaving neighboring bacteria and human cells unharmed. On the other hand, this has been one of the most prominent flaws of antibiotics, like bombs they kill every bacterium in their target vicinity; even the good ones like Clostridium butyricum. C. butyricum is one of the good bacteria found in our gut, which produces compounds like butyrate that are beneficial for humans and protects them from harmful diseases. Experiments conducted by Zheng et al. showed that C. butyricum suppressed the growth of CRC cells and helped kill them by producing butyrate. But when antibiotics were used to kill the bad guys; F. nucleatum they also killed C. butyricum as well. This showed that a new therapy needs to be designed that only kills the bad bacteria and not the good one.
For this purpose, P2 phages isolated from human saliva were used that specifically killed F. nucleatum. P2 phage specificity was confirmed by testing its killing powers on five different kinds of bacteria and it ultimately chose to kill only F. nucleatum. But since we were going to introduce this phage in our body where a lot of other bacteria’s and organisms live, we needed to be sure it only killed F. nucleatum inside our body too. So, these P2 phages were used to infect tumor samples taken from patients of CRC, the results revealed that only F.nucleatum was targeted.
This discovery opened a new horizon in CRC treatment, as not only these phages killed F. nucleatum but could also be used to specifically target the tumor cells with drugs as both the bad guys; F. nucleatum and cancer cells resided near each other in our gut. After getting to know this Zheng et al like ’Professor Utonium’ set out to find the perfect nanoparticles that could be used with our powerpuff phages to kill both the Mojo JoJo’s: bacteria and cancer cells. Nanoparticles are particles that are very, very small having a size in the range of 1-100 nanometer. The superhero selected to aid our powerpuff phages was Dextrose Nanoparticles (DNPs), which would hold the weapon Irinotecan (IDNP) that would be used to destroy cancer cells. In addition to having a super weapon, DNPs also boosted the good bacteria C. butyricum and helped them fight off Cancer cells.
Various test battles were held between our super heroes: P2 Phages, The IDNP, C. butyricum and the Evil forces: Colorectal cancer cells and F. nucleatum in mouse and pigs. All the battles were won by our superheroes as they showed significant decrease in evil cancer cell and F. nucleatum population.
This episode of Powerpuff phages, shows the potential of phages not only being used as a therapy against bacterial infections but also reveal a new therapy where phage guided nanoparticles can be used to deliver drugs to target cell.
Original article: Zheng, D.-W. et al. Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy. Nat. Biomed.Eng. https://doi.org/10.1038/s41551-019-0423-2 (2019)
My name is Azka Yamin and I am doing BS Applied Bioscience(currently in final year). I have been doing content writing for the past 3 years and science communication has become my passion in the past few years. Many people outside of the biology field are unaware of even the basics. My aim is to make biological research understandable to all by explaining it in simple words.
Azka Yamin, Student BS Applied Biosciences. Atta-Ur-Rahman School of Applied Biosciences, National University of Science and Technology (NUST), Islamabad, Pakistan.