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Team:Montpellier/Phages

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PHAGES



Phages are at the heart of our project. They are viruses that can only infect bacteria and are benign for humans. This property makes them very interesting in medicine as they can kill bacteria without harming us. From that was born phage therapy in the early 20th century.
There is an extreme diversity of phages, scientists said that we would have sampled only 0.0002% of phages metagenomes. There would be 10 phages for 1 bacteria on earth which makes them the most abundant organisms.

Each phage has its own properties:

  1. The genetic information can be RNA or DNA, double stranded or single stranded (positive or negative), circular or linear and from very various lengths.
  2. They can harbour different shapes: filamentous or with a icosahedral head and a tail more or less long.


There are three main types of life cycle [1]: the first one is the lytic cycle. The phage injects its genome into a host bacterium. If its genome is RNA it will first be transcribed by reverse transcriptase in DNA. Then it will be replicated and translated creating new phages; when a great amount of phages is stored in the cell, they produce lysine and exit the host making holes in its membrane and killing it. The second life cycle is lysogeny. Like for the first one, the phage injects its genome but it stays still, integrates the bacterial chromosome, and replicates with it. It can turn into a lytic strategy depending on certain conditions and then reproduce. Phages that can make both life cycles are called temperate phages. The last life cycle, we could call chronic, is a life cycle in which phages reproduce in the host: the DNA is transcribed and translated but the phages exit continuously the cell without killing it. In our project, we need to select phages with a life cycle adapted in order to produce proteins of interest and not kill all the bacteria population.

The last property of phages that is very important for the treatment is specificity: each phage can infect one type of bacteria. As each cancer microbiome depends on its localization, a single phage is not adapted to all cancer treatments (see Microbiome). Thus Phagent is a general concept rather than a ubiquitous treatment. Each type of cancer requires a specific design of Phagent.

Some phages are a lot more used in scientific research, they often infect Escherichia coli, and we know a lot more about them than others. It is the case for phage λ or M13. Those might be interesting for the pancreas cure as we know that E. coli migrates from gut to pancreas tumors.

Concerning the prostate, where the major genus is Propionibacterium, phage 174 has been identified and it has been shown that a lot of Propionibacterium infecting phages are found in cheese. It is an important fact as it shows that phages are available close to us and the research to find the right one is not too utopian. [2]

In colorectal cancer, there are a lot of different bacteria. That means a lot of potential targets. The best way to find weapons against those targets is to study phages that are already there, because, where bacteria are present, phages are present too, and this is even more true in the intestines than everywhere. [3]

For lung cancer, phages have been identified for the genus Veillonella: there are 25 types of phages and three, in particular, have been studied. They are N2, N11, and N20. [4]

The last cancer presented in section Microbiome is ovary cancer and its Pediococcus microbiome. A phage identified that infects bacteria of this genus is clP1. However we can’t be sure that the strain present in the ovary cancer microbiome can actually be infected by this phage. [5][6]




Table 1: Group of phage for a specific bacterium.
Organ Bacteria genus Phage
Prostate Propionibacterium Phage 174
Colon Rectal and distal: Alistipes, Akkermansia, Halomonas and Shewanella.

Proximal: Faecalibacterium, Blautia and Clostridium.
/
Lung Veillonella and Megasphaera Phage N2, N11 and N20
Ovary Pediococcus cIP
Pancreas Pseudomonas putida PF16 and phiPMW [7]




References

[1] Janine trempy and Nancy Trun. Fundamental Bacterial Genetics. Chapter 7 : bacteriophages. (2004)
[2] Holger Brüggemann and Rolf Lood. Bacteriophages infecting Propionibacterium acnes. BioMed research international (11 April 2013)
[3] Breck A. Duerkop et al. Murine colitis reveals a disease-associated bacteriophage community. Nature microbiology. (23 January 2013)
[4] Szymon P. Szafranski et al. The use of bacteriophages to biocontrol oral biofilms. Journal of biotechnology. (20 May 2017)
[5] Ifigeneia Kyrkou et al. Isolation and characterization of novel phages infecting Lactobacillus plantarum and proposal of new genus, ‘Silenusvirus’. Scientific reports. (29 May 2020)
[6] David Kelly et al. Genome sequance of the phage clP1, which infects the beer spoilage bacterium Pediococcus damnosius. Gene. (1 August 2012)
[7] “Pf16 and phiPMW: Expanding the realm of Pseudomonas putida bacteriophages” by Damian J. Magill in Plos one, 2017