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Bacteriophages, or phages for short, are viruses that infect bacteria and hijack bacterial cellular machinery to reproduce themselves. Phages are extremely abundant entities, and could be responsible for up to 20-40% of bacterial mortality daily (Hampton et al., 2020). Therefore, phage infection constitutes a very strong evolutionary pressure for bacteria.
Bacteriophages, or phages for short, are viruses that infect bacteria and hijack bacterial cellular machinery to reproduce themselves. Phages are extremely abundant entities, and could be responsible for up to 20-40% of bacterial mortality daily :ref{doi=10.1038/s41586-019-1894-8}. Therefore, phage infection constitutes a very strong evolutionary pressure for bacteria.
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The sighting of a second defense system occured more than 40 years later, in the late 1980s, when several teams around the world observed arrays containing short, palindromic DNA repeats clustered together on the bacterial genome (Barrangou et al., 2017). Yet, the biological function of these repeats was only elucidated in 2007, when a team of researchers demonstrated that these repeats were part of a new anti-phage defense systems (Barrangou et al., 2007) , known as [CRISPR-Cas system](https://en.wikipedia.org/wiki/CRISPR).
The sighting of a second defense system occured more than 40 years later, in the late 1980s, when several teams around the world observed arrays containing short, palindromic DNA repeats clustered together on the bacterial genome (Barrangou et al., 2017). Yet, the biological function of these repeats was only elucidated in 2007, when a team of researchers demonstrated that these repeats were part of a new anti-phage defense systems :ref{doi=10.1126/science.1138140}, known as [CRISPR-Cas system](https://en.wikipedia.org/wiki/CRISPR).
Following these two major breakthroughs, knowledge of anti-phage systems remained scarce for some years. Yet, in 2011, Makarova and colleagues revealed that anti-phage systems tend to colocalize on the bacterial genome in defense-islands. This led to a guilt-by-association hypothesis : if a gene or a set of genes is frequently found in bacterial genomes in close proximity to known defense systems, such as RM or CRISPR-Cas systems, then it might constitute a new defense system. This concept had a large role in the discovery of an impressive diversity of defense systems in a very short amount of time. To date, more than 60 defense systems have been described.
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Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.