@@ -25,16 +25,15 @@ In response to this evolutionary pressure, bacteria have developed an arsenal of
## History
The first anti-phage defense system was discovered in the early 1950s by two separate teams of researchers (Luria and Human, 1952 ; Bertani and Wiegle 1952). Luria and Human reported a mysterious phenomenon, where one phage was only capable of infecting a specific bacterial strain once. The progeny phages produced by this first round of infection had lost their ability to infect the same strain again, yet remained able to infect other bacterial strains. For them, this could only mean that "the genotype of the host in which a virus reproduces affects the phenotype of the new virus" (Luria and Human, 1952). A similar phenomenon was shortly after described by Bertani and Wiegle.
The first anti-phage defense system was discovered in the early 1950s by two separate teams of researchers :ref{doi=10.1128/jb.64.4.557-569.1952}, :ref{doi=10.1128/jb.65.2.113-121.1953}. Luria and Human reported a mysterious phenomenon, where one phage was only capable of infecting a specific bacterial strain once. The progeny phages produced by this first round of infection had lost their ability to infect the same strain again, yet remained able to infect other bacterial strains. For them, this could only mean that "the genotype of the host in which a virus reproduces affects the phenotype of the new virus" :ref{doi=10.1128/jb.64.4.557-569.1952}. A similar phenomenon was shortly after described by Bertani and Wiegle.
Their work was in fact the first report of what would later be named Restriction-Modification ([RM](/defense-systems/rm)) system, which is considered to be the first anti-phage defense system discovered.
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).
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 :ref{doi=10.1038/nmicrobiol.2017.92}. 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.
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 :ref{doi=10.1128/JB.05535-11}. 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.
## List of known defense systems
To date, more than 60 anti-phage defense systems have been described. An exhaustive list of the systems with experimentally validated anti-phage activity can be found [here](/defense-systems).
To date, more than 150 anti-phage defense systems have been described. An exhaustive list of the systems with experimentally validated anti-phage activity can be found [here](/defense-systems).
