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...@@ -25,7 +25,7 @@ Bacteria and their phages have co-existed for billions of years. The pressure of ...@@ -25,7 +25,7 @@ Bacteria and their phages have co-existed for billions of years. The pressure of
The first discovered anti-phage system, a Restriction-Modification (RM) system, was described in the early 1950s :ref{doi=10.1128/jb.64.4.557-569.1952,10.1128/jb.65.2.113-121.1953}. In the following decades, a handful of other systems were discovered :ref{doi=10.1016/j.mib.2005.06.006}. In 2007, CRISPR-Cas systems were discovered to be anti-phage systems :ref{doi=10.1126/science.1138140}. As CRISPR-Cas systems and RM systems are extremely prevalent in bacteria, it was thought for some years that the antiviral immune system of bacteria had been mostly elucidated. The first discovered anti-phage system, a Restriction-Modification (RM) system, was described in the early 1950s :ref{doi=10.1128/jb.64.4.557-569.1952,10.1128/jb.65.2.113-121.1953}. In the following decades, a handful of other systems were discovered :ref{doi=10.1016/j.mib.2005.06.006}. In 2007, CRISPR-Cas systems were discovered to be anti-phage systems :ref{doi=10.1126/science.1138140}. As CRISPR-Cas systems and RM systems are extremely prevalent in bacteria, it was thought for some years that the antiviral immune system of bacteria had been mostly elucidated.
Following these two major breakthroughs, knowledge of anti-phage systems remained scarce for some years. Yet, in 2011, it was 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 hypothesis was tested systematically in a landarmark study in 2018 :ref{doi=10.1126/science.aar4120} leading to the discovery of 10 novel anti-phage systems. This started the uncovering of an impressive diversity of defense systems in a very short amount of time :ref{doi=10.1038/s41579-023-00934-x}. Following these two major breakthroughs, knowledge of anti-phage systems remained scarce for some years. Yet, in 2011, it was 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 near known defense systems, such as RM or CRISPR-Cas systems, then it might constitute a new defense system. This hypothesis was tested systematically in a landmark study in 2018 :ref{doi=10.1126/science.aar4120} leading to the discovery of 10 novel anti-phage systems. This started the uncovering of an impressive diversity of defense systems in a very short amount of time :ref{doi=10.1038/s41579-023-00934-x}.
To date over 150 types of defense systems have been described, unveiling an unsuspected diversity of molecular mechanisms. The antiviral immune systems of bacteria therefore appear much more complex than previously envisioned, and new discoveries do not seem to be slowing down. To date over 150 types of defense systems have been described, unveiling an unsuspected diversity of molecular mechanisms. The antiviral immune systems of bacteria therefore appear much more complex than previously envisioned, and new discoveries do not seem to be slowing down.
...@@ -35,6 +35,6 @@ The fast pace of discoveries in the field can be intimidating to newcomers and c ...@@ -35,6 +35,6 @@ The fast pace of discoveries in the field can be intimidating to newcomers and c
1. A “general concepts” section, introducing key notions and ideas to understand anti-phage defense 1. A “general concepts” section, introducing key notions and ideas to understand anti-phage defense
2. A section introducing succinctly each of the defense systems currently known. 2. A section introducing succinctly each of the defense systems currently known.
This wiki is only a first version, and is intended to evolve based on the ideas and needs of the people using it. Whether it is to suggest new pages or to edit existing ones, all contributions are more than welcomed: please do not hesitate to contact us to participate! This wiki is only a first version and is intended to evolve based on the ideas and needs of the people using it. Whether it is to suggest new pages or to edit existing ones, all contributions are more than welcome: please do not hesitate to contact us to participate!
...@@ -17,14 +17,14 @@ Analyses are kept for 6 months, or with a maximum of 10 jobs. ...@@ -17,14 +17,14 @@ Analyses are kept for 6 months, or with a maximum of 10 jobs.
![webservice_interface](/help/webservice_interface.jpg){max-width=750px} ![webservice_interface](/help/webservice_interface.jpg){max-width=750px}
In the Analyses panel, each past job is kept for 6 months. Next to the name of the input file (1) there is a rolling circle until the job finishes to run, which become a number. One can edit the job name (by default it's the file's name) by clicking on the small pen (2), or can delete a job (3). To visualize the results, one can click on Results (4) or on the job's name. In the Analyses panel, each past job is kept for 6 months. Next to the name of the input file (1) there is a rolling circle until the job finishes running, which becomes a number. One can edit the job name (by default it's the file's name) by clicking on the small pen (2), or can delete a job (3). To visualize the results, one can click on Results (4) or on the job's name.
![analyses_interface](/help/analyses_interface.jpg){max-width=750px} ![analyses_interface](/help/analyses_interface.jpg){max-width=750px}
The result consists in 3 tables : The result consists of 3 tables :
- Systems table: Shown by default. One system per line. On the column type, there is the name of the system, and one can click on it to be redirected to the corresponding wiki page (1). - Systems table: Shown by default. One system per line. On the column type, there is the name of the system, and one can click on it to be redirected to the corresponding wiki page (1).
- Genes table (2): One gene per line. Those are genes from the aforementioned system, with some addition information on the quality of the hit. The key between both table is `sys_id` - Genes table (2): One gene per line. Those are genes from the aforementioned system, with some addition information on the quality of the hit. The key between both tables is `sys_id``
- HMMER table (3): One gene per line. Here it's all the genes hit by a hmm profile, even when the gene is not part of a defense system. - HMMER table (3): One gene per line. Here it's all the genes hit by a hmm profile, even when the gene is not part of a defense system.
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...@@ -7,10 +7,10 @@ layout: article ...@@ -7,10 +7,10 @@ layout: article
## 1/ Create an account ## 1/ Create an account
The wiki is based on gitlab pages, and we are using the gitlab's instance of the Pasteur Institute. To contribute, users need to be part of the project. The wiki is based on GitLab pages, and we are using the GitLab's instance of the Pasteur Institute. To contribute, users need to be part of the project.
On every page, there is a button at the bottom proposing to "Edit on Gitlab". It will allow anyone registered to edit a given page seamlessly. On every page, there is a button at the bottom proposing to "Edit on GitLab". It will allow anyone registered to edit a given page seamlessly.
But on the first try, the following dialog will be prompted. If you have a Pasteur account, chose 1, otherwise chose 2. In External account, you can connect with a third-party account such as Github, bitbucket or google. But on the first try, the following dialog will be prompted. If you have a Pasteur account, choose 1, otherwise choose 2. In an External account, you can connect with a third-party account such as Github, bitbucket or Google.
If you have neither, register on Github first (it's always useful). If you have neither, register on Github first (it's always useful).
![Register](/help/register_1.png){max-width=750px} ![Register](/help/register_1.png){max-width=750px}
...@@ -19,25 +19,25 @@ Once your account is created, you need to request access to the project, on the ...@@ -19,25 +19,25 @@ Once your account is created, you need to request access to the project, on the
![Request Access](/help/Request_access.png){max-width=600px} ![Request Access](/help/Request_access.png){max-width=600px}
Click, and wait for an admin approval. Click, and wait for admin approval.
## 2/ Edit a page ## 2/ Edit a page
Once you have access to the project (the previous step is done once), you can edit easily each page of the wiki, and post [issues](https://gitlab.pasteur.fr/mdm-lab/wiki/-/issues) (if you have question about something or remarks with anything from content to design). Once you have access to the project (the previous step is done once), you can edit easily each page of the wiki, and post [issues](https://gitlab.pasteur.fr/mdm-lab/wiki/-/issues) (if you have questions about something or remarks with anything from content to design).
To edit a page, just click on the Edit on Gitlab button at the bottom of every page of the wiki, and it will lead you to the corresponding page of the wiki. To edit a page, just click on the Edit on GitLab button at the bottom of every page of the wiki, and it will lead you to the corresponding page of the wiki.
From this page, you can : From this page, you can :
1. Edit the text you'd like 1. Edit the text you'd like
2. Preview the change you've done (final modification might a bit different, especially if you use plugins to view citations or pdb structures) 2. Preview the change you've done (the final modification might be a bit different, especially if you use plugins to view citations or PDB structures)
3. Once you've finished you edits, you can specify what you did (e.g. "Re-wrote history of defense systems") 3. Once you've finished your edits, you can specify what you did (e.g. "Re-wrote history of defense systems")
4. This field is for the branch name, you can let it with the default value, or specify a more meaningful name (note that it's good to have your user name in the branch name so we can) 4. This field is for the branch name, you can leave it with the default value, or specify a more meaningful name (note that it's good to have your user name in the branch name so we can)
![Edit a page](/help/Edit_page.png){max-width=750px} ![Edit a page](/help/Edit_page.png){max-width=750px}
Then it asks you to create a merge request. Then it asks you to create a merge request.
In other words, the modifications you made will not be reflected on the website until a few automatic checks passed (which should be ok since you modified only some text) and that another person reviewed the change, and accept the merge request. In other words, the modifications you made will not be reflected on the website until a few automatic checks passed (which should be ok since you modified only some text) and another person reviewed the change, and accepted the merge request.
To do so, just fill in the description (1) of what you did, or anything that you would like the person who will accept the merge request to know, and just hit (2) "Create a merge request". To do so, just fill in the description (1) of what you did, or anything that you would like the person who will accept the merge request to know, and just hit (2) "Create a merge request".
...@@ -45,9 +45,9 @@ To do so, just fill in the description (1) of what you did, or anything that you ...@@ -45,9 +45,9 @@ To do so, just fill in the description (1) of what you did, or anything that you
## 3/ Tips to write Markdown ## 3/ Tips to write Markdown
As a general advice, check an already written file to see how other pages are written.<br><br> As general advice, check an already written file to see how other pages are written.<br><br>
The files you edit are in markdown, which is pretty basic language but that can let you do many things, such as tables, links and such with a particular syntax. The files you edit are in markdown, which is a pretty basic language that can let you do many things, such as tables, links and such with a particular syntax.
You can check more about this syntax here: <https://docs.gitlab.com/ee/user/markdown.html><br><br> You can check more about this syntax here: <https://docs.gitlab.com/ee/user/markdown.html><br><br>
To add images, you need to upload the image in the `/content/public` folder (and possibly in the corresponding folder of the defense system) To add images, you need to upload the image in the `/content/public` folder (and possibly in the corresponding folder of the defense system)
...@@ -61,7 +61,7 @@ where `/path/within/public` is the relative path to the `public` folder (the abs ...@@ -61,7 +61,7 @@ where `/path/within/public` is the relative path to the `public` folder (the abs
In addition to this, there are some specificities to this wiki :<br><br> In addition to this, there are some specificities to this wiki :<br><br>
**1. Each system's page has *frontmatter*, which is a piece of code that will be used to populate the table of the list of system. It has the following syntax :** **1. Each system's page has *frontmatter*, which is a piece of code that will be used to populate the table of the list of systems. It has the following syntax :**
```yaml ```yaml
--- ---
...@@ -106,7 +106,7 @@ This part is a bit tricky to edit. Your first option is to create an issue or se ...@@ -106,7 +106,7 @@ This part is a bit tricky to edit. Your first option is to create an issue or se
The second option is that you can try within this live editor : https://mermaid.live/ The second option is that you can try within this live editor : https://mermaid.live/
You can copy paste everything that is within `<mermaid></mermaid>` tags in the editor field of the [live editor](https://mermaid.live/), it should reproduce what you site on the website. From there you can try to modify it until you get what you want. You can copy paste everything that is within `<mermaid></mermaid>` tags in the editor field of the [live editor](https://mermaid.live/), it should reproduce what you site on the website. From there you can try to modify it until you get what you want.
Here is the documentation about mermaid (the software behind this syntax) : https://mermaid.js.org/intro/ Here is the documentation about Mermaid (the software behind this syntax): https://mermaid.js.org/intro/
**Custom containers:** **Custom containers:**
...@@ -186,9 +186,9 @@ This is an info box ...@@ -186,9 +186,9 @@ This is an info box
### 4/ Review a Merge Request ### 4/ Review a Merge Request
You can review other person's merge request by going the [merge request's pages](https://gitlab.pasteur.fr/mdm-lab/wiki/-/merge_requests). You can review other people's merge requests by going to the [merge request](https://gitlab.pasteur.fr/mdm-lab/wiki/-/merge_requests)'s pages](https://gitlab.pasteur.fr/mdm-lab/wiki/-/merge_requests).
On a given page, you can see what modifications where made for this merge request (1), then you can comment if you have anything to say (2 and 3). On a given page, you can see what modifications were made for this merge request (1), and then you can comment if you have anything to say (2 and 3).
And finally, you can approve (4) the MR if you find it worth publishing on the website. And finally, you can approve (4) the MR if you find it worth publishing on the website.
![review a MR](/help/Review_MR.png){max-width=750px} ![review a MR](/help/Review_MR.png){max-width=750px}
...@@ -197,8 +197,8 @@ If you want to modify further the file or other file within the same merge reque ...@@ -197,8 +197,8 @@ If you want to modify further the file or other file within the same merge reque
![Edit_MR](/help/Edit_MR.png){max-width=750px} ![Edit_MR](/help/Edit_MR.png){max-width=750px}
The Web IDE editor allows you to edit multiple file at once for a given commit. This editor is also accessible from the merge request's page under the "Code" button in the upper right corner of the page. The Web IDE editor allows you to edit multiple files at once for a given commit. This editor is also accessible from the merge request's page under the "Code" button in the upper right corner of the page.
## Contribute to the code ## Contribute to the code
Contribution to the code and design are open. Please read the [README](https://gitlab.pasteur.fr/mdm-lab/wiki) on how to deploy the website locally (and see the modification you're doing live). Contribution to the code and design is open. Please read the [README](https://gitlab.pasteur.fr/mdm-lab/wiki) on how to deploy the website locally (and see the modification you're doing live).
...@@ -31,7 +31,7 @@ Controlled cell death upon detection of the phage infection stops the propagatio ...@@ -31,7 +31,7 @@ Controlled cell death upon detection of the phage infection stops the propagatio
:ref{doi=10.1016/S0960-9822(00)00124-X,10.1016/j.mib.2005.06.006}. :ref{doi=10.1016/S0960-9822(00)00124-X,10.1016/j.mib.2005.06.006}.
Abortive infection can thus be thought of as a form of bacterial altruism. Abortive infection can thus be thought of as a form of bacterial altruism.
With the recent developments in phage-defense systems and microbial immunity (see :ref{doi=10.1038/s41579-023-00934-x} for a review), many newly identifed anti-phage defense systems are thought to function through abortive infection. Abortive defense systems often detect the phage infection at the later stage through protein sensing or the monitoring of host integrity but can also be based on nucleic acid sensing. Upon sensing, a diverse set of effectors can be used to reduce metabolism or induce cell-death (e.g., NAD+ depletion, translation interruption or membrane depolarisation). The diversity of and mechanisms of abortive infection were recently reviewd here :ref{doi=10.1146/annurev-virology-011620-040628}, while the evolutionary success of this paradoxical altruistic form of immunity has recently been discussed here :ref{doi=10.1016/j.mib.2023.102312}. With the recent developments in phage-defense systems and microbial immunity (see :ref{doi=10.1038/s41579-023-00934-x} for a review), many newly identified anti-phage defense systems are thought to function through abortive infection. Abortive defense systems often detect the phage infection at a later stage through protein sensing or the monitoring of host integrity but can also be based on nucleic acid sensing. Upon sensing, a diverse set of effectors can be used to reduce metabolism or induce cell-death (e.g., NAD+ depletion, translation interruption or membrane depolarisation). The diversity of and mechanisms of abortive infection were recently reviewed here :ref{doi=10.1146/annurev-virology-011620-040628}, while the evolutionary success of this paradoxical altruistic form of immunity has recently been discussed here :ref{doi=10.1016/j.mib.2023.102312}.
Although abortive infection is currently often understood as leading to cell-death, it should be noted that its original definition appeared to be broader and that some mechanisms currently included as abortive infection may only lead to metabolic stalling or dormancy. Although abortive infection is currently often understood as leading to cell-death, it should be noted that its original definition appeared to be broader and that some mechanisms currently included as abortive infection may only lead to metabolic stalling or dormancy.
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...@@ -12,12 +12,12 @@ Upon phage infection, the bacterial immune system senses a specific phage compon ...@@ -12,12 +12,12 @@ Upon phage infection, the bacterial immune system senses a specific phage compon
## Diversity ## Diversity
Various determinants of the phage can elicit bacterial immunity either in a direct or indirect manner. The most common and well known prokaryotic anti-phage systems, restriction enzymes and CRISPR-Cas, recognize and cleave phage DNA or RNA. More recently, a CBASS system has been found to directly bind to a structured phage RNA that triggers immune activation :ref{doi=10.1101/2023.03.07.531596}. In other cases, defense systems are activated by protein coding phage genes. In some cases, the phage protein is directly sensed by the defense systems, as has been beautifully demonstrated for the Avs systems that directly bind either the phage terminase or portal protein :ref{doi=10.1126/science.abm4096}. In other cases, the phage protein can be sensed indirectly by the defense system, for example by detecting its activity in the cell. Such an indirect mechanism has been found for example in the case of some retron defense systems that are triggered by phage tampering with the RecBCD protein complex :ref{doi=10.1016/j.cell.2020.09.065,10.1016/j.cell.2023.02.029}. For a comprehensive coverage of all recent phage detection mechanisms the recent review by Huiting and Bondy-Denomy :ref{doi=10.1016/j.mib.2023.102325} is highly recommended. Various determinants of the phage can elicit bacterial immunity either in a direct or indirect manner. The most common and well-known prokaryotic anti-phage systems, restriction enzymes and CRISPR-Cas recognize and cleave phage DNA or RNA. More recently, a CBASS system has been found to directly bind to a structured phage RNA that triggers immune activation :ref{doi=10.1101/2023.03.07.531596}. In other cases, defense systems are activated by protein-coding phage genes. In some cases, the phage protein is directly sensed by the defense systems, as has been beautifully demonstrated for the Avs systems that directly bind either the phage terminase or portal protein :ref{doi=10.1126/science.abm4096}. In other cases, the phage protein can be sensed indirectly by the defense system, for example by detecting its activity in the cell. Such an indirect mechanism has been found for example in the case of some retron defense systems that are triggered by phage tampering with the RecBCD protein complex :ref{doi=10.1016/j.cell.2020.09.065,10.1016/j.cell.2023.02.029}. For comprehensive coverage of all recent phage detection mechanisms, the recent review by Huiting and Bondy-Denomy :ref{doi=10.1016/j.mib.2023.102325} is highly recommended.
## Method of discovery: ## Method of discovery:
The main method used to pinpoint phage components that trigger a specific defense system of interest has been through a simple classic genetics approach, whereby mutant phages that overcome the defense system are examined. Such mutants often occur spontaneously and can thus be selected for by simply picking phage plaques that are able to form on a lawn of bacteria expressing the defense system :ref{doi=10.1016/j.cell.2023.02.029,10.1016/j.mib.2023.102325}. The hypothesis is that the phage mutant escapes bacterial immunity due to a mutation in the component sensed by the system. Thus, sequencing these phage mutants and identification of the mutated locus is the first required step. To validate that the mutated phage component is indeed the actual trigger of the defense system, follow up experiments are required. For example, in some cases expression of this phage component without any other phage genes is sufficient to elicit the activity of bacterial immune system. This approach was used to identify Borvo activation by expression of the phage DNA polymerase, Dazbog activation by expression of a phage DNA methylase, retron activation by either phage SSB proteins :ref{doi=10.1016/j.cell.2023.02.029} or by proteins that inhibit the host RecBCD3, CapRel triggering by the phage Capsid protein :ref{doi=10.1038/s41586-022-05444-z} and many more :ref{doi=10.1016/j.mib.2023.102325}. Additional biochemical pulldown assays can be used to assess binding of the defense system to the suspected phage trigger. The main method used to pinpoint phage components that trigger a specific defense system of interest has been through a simple classic genetics approach, whereby mutant phages that overcome the defense system are examined. Such mutants often occur spontaneously and can thus be selected for by simply picking phage plaques that are able to form on a lawn of bacteria expressing the defense system :ref{doi=10.1016/j.cell.2023.02.029,10.1016/j.mib.2023.102325}. The hypothesis is that the phage mutant escapes bacterial immunity due to a mutation in the component sensed by the system. Thus, sequencing these phage mutants and identification of the mutated locus is the first required step. To validate that the mutated phage component is indeed the actual trigger of the defense system, follow up experiments are required. For example, in some cases, expression of this phage component without any other phage genes is sufficient to elicit the activity of the bacterial immune system. This approach was used to identify Borvo activation by expression of the phage DNA polymerase, Dazbog activation by expression of a phage DNA methylase, retron activation by either phage SSB proteins :ref{doi=10.1016/j.cell.2023.02.029} or by proteins that inhibit the host RecBCD3, CapRel triggering by the phage Capsid protein :ref{doi=10.1038/s41586-022-05444-z} and many more :ref{doi=10.1016/j.mib.2023.102325}. Additional biochemical pulldown assays can be used to assess the binding of the defense system to the suspected phage trigger.
One major caveat in the above approach is that in some cases mutant phages that escape the immune system cannot be isolated. This can occur for example if the defense system senses a general fold of a highly conserved and essential phage protein. In this case a simple mutation in the protein will not suffice for the phage to escape detection. In such cases, an alternative approach can be used that does not rely on isolation of escape mutants. An overexpression library of all phage genes can be co-expressed with the defense system of interest, and then assayed for immune activation. This approach was successfully applied for identification phage components that trigger diverse Avs systems :ref{doi=10.1126/science.abm4096}. One major caveat in the above approach is that in some cases mutant phages that escape the immune system cannot be isolated. This can occur for example if the defense system senses a general fold of a highly conserved and essential phage protein. In this case, a simple mutation in the protein will not suffice for the phage to escape detection. In such cases, an alternative approach can be used that does not rely on isolation of escape mutants. An overexpression library of all phage genes can be co-expressed with the defense system of interest and then assayed for immune activation. This approach was successfully applied for the identification of phage components that trigger diverse Avs systems :ref{doi=10.1126/science.abm4096}.
## General concepts ## General concepts
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...@@ -19,8 +19,7 @@ The effector components of anti-phage systems are very diverse, and can be arbit ...@@ -19,8 +19,7 @@ The effector components of anti-phage systems are very diverse, and can be arbit
## Nucleic-acid-degrading effectors. ## Nucleic-acid-degrading effectors.
Many defense systems target (either through cleavage or modification) nucleic acids to mediate the immune response. Many defense systems target (either through cleavage or modification) nucleic acids to mediate the immune response.
These nucleic acids targeting systems are divided between systems that specifically target phage nucleic acids to stop These nucleic acid-targeting systems are divided between systems that specifically target phage nucleic acids to stop phage replication, and systems that untargetedly affect bacterial and viral nucleic acids to halt the growth of both the
phage replication, and systems that untargetedly affect bacterial and viral nucleic acids to halt the growth of both the
infected host and the phage. infected host and the phage.
Nucleic-acid-degrading systems include [RM](/defense-systems/rm), [CRISPR-Cas](/defense-systems/cas), [Ssp](/defense-systems/sspbcde) and [Ddn](/defense-systems/dnd), certain types of [CBASS](/defense-systems/cbass), [Avs](/defense-systems/avs) and [Lamassu](/defense-systems/lamassu-fam), [PrrC](/defense-systems/prrc), [RloC](/defense-systems/rloc)... Nucleic-acid-degrading systems include [RM](/defense-systems/rm), [CRISPR-Cas](/defense-systems/cas), [Ssp](/defense-systems/sspbcde) and [Ddn](/defense-systems/dnd), certain types of [CBASS](/defense-systems/cbass), [Avs](/defense-systems/avs) and [Lamassu](/defense-systems/lamassu-fam), [PrrC](/defense-systems/prrc), [RloC](/defense-systems/rloc)...
...@@ -38,4 +37,4 @@ They include for instance bacterial Gasdermins, RexAB, Pif, AbiZ, certain types ...@@ -38,4 +37,4 @@ They include for instance bacterial Gasdermins, RexAB, Pif, AbiZ, certain types
## Other types of effectors. ## Other types of effectors.
Finally, some types of less prevalent effectors were not included into these broad categories. This includes protein modifying effectors, and some chemical defense systems. Finally, some types of less prevalent effectors were not included in these broad categories. This includes protein-modifying effectors and some chemical defense systems.
...@@ -10,7 +10,7 @@ contributors: ...@@ -10,7 +10,7 @@ contributors:
Anti-phage defense systems have been discovered through various research methodologies and scientific investigations. Anti-phage defense systems have been discovered through various research methodologies and scientific investigations.
The first defense systems that were discovered and characterized were restriction modifications (RM) and CRISPR-cas systems, in the 1960s and early 2000s respectively. These systems are the most abundantly encoded in prokaryotic genomes and were discovered by researchers that observed heritable bacterial resistance of certain strains to bacteriophages. A combination of functional studies, bacterial genetics, and biochemical assays enabled to elucidate their mechanisms of action, leading to the development of tools that revolutionized molecular biology and genetic engineering. The first defense systems that were discovered and characterized were restriction modifications (RM) and CRISPR-cas systems, in the 1960s and early 2000s respectively. These systems are the most abundantly encoded in prokaryotic genomes and were discovered by researchers who observed heritable bacterial resistance of certain strains to bacteriophages. A combination of functional studies, bacterial genetics, and biochemical assays enabled to elucidate of their mechanisms of action, leading to the development of tools that revolutionized molecular biology and genetic engineering.
In recent years, the discovery and characterization of dozens of novel anti-phage defense systems involve a combination of bioinformatics, genomics analysis and experimental approaches. The computational pipeline that has allowed to identify and validate numerous systems in the past years is based on the observation that anti-phage defense systems tend to co-localize on prokaryotic chromosomes in regions denoted as defense islands. Using this principle, recent studies have discovered more than 150 novel systems, by identifying and testing single or multi protein uncharacterized systems that are enriched within such defense islands. Candidate systems are typically cloned into heterologous expression hosts, to validate their anti-phage function. The mechanisms of many these newly discovered systems remain unknown. In recent years, the discovery and characterization of dozens of novel anti-phage defense systems involve a combination of bioinformatics, genomics analysis and experimental approaches. The computational pipeline that has allowed to identify and validate numerous systems in the past years is based on the observation that anti-phage defense systems tend to co-localize on prokaryotic chromosomes in regions denoted as defense islands. Using this principle, recent studies have discovered more than 150 novel systems, by identifying and testing single or multi-protein uncharacterized systems that are enriched within such defense islands. Candidate systems are typically cloned into heterologous expression hosts, to validate their anti-phage function. The mechanisms of many of these newly discovered systems remain unknown.
...@@ -11,8 +11,8 @@ contributors: ...@@ -11,8 +11,8 @@ contributors:
# Defense Islands # Defense Islands
**Defense islands** are regions of prokaryotic genomes enriched in defense systems. Their existence first described in Makarova *et al.* :ref{doi=10.1128/JB.05535-11}, who observed that genes encoding defense systems (mainly Restriction Modification enzymes, Toxin-Antitoxin systems, but notably not CRISPR) tended to cluster preferentially on specific portions of bacterial genomes. They postulated that unknown genes commonly found associated to these regions would likely have a defensive role themselves, and confirmed bioinformatically that many of them were indeed diverged versions of classical defense systems. Other systems of genes commonly found in defense islands were later isolated and heterologously expressed to experimentally confirm to have a defensive role (BREX, DISARM). Doron *et al.* :ref{doi=10.1126/science.aar4120}, later followed by Millmann *et al.* :ref{doi=10.1016/j.chom.2022.09.017}, used the colocalization of genes in defense islands to generate many candidate systems and test them experimentally in high throughput screens, leading to the discovery of a large number of new defense systems. **Defense islands** are regions of prokaryotic genomes enriched in defense systems. Their existence was first described in Makarova *et al.* :ref{doi=10.1128/JB.05535-11}, who observed that genes encoding defense systems (mainly Restriction Modification enzymes, Toxin-Antitoxin systems, but notably not CRISPR) tended to cluster preferentially on specific portions of bacterial genomes. They postulated that unknown genes commonly found associated with these regions would likely have a defensive role themselves, and confirmed bioinformatically that many of them were indeed diverged versions of classical defense systems. Other systems of genes commonly found in defense islands were later isolated and heterologously expressed to experimentally confirm to have a defensive role (BREX, DISARM). Doron *et al.* :ref{doi=10.1126/science.aar4120}, later followed by Millmann *et al.* :ref{doi=10.1016/j.chom.2022.09.017}, used the colocalization of genes in defense islands to generate many candidate systems and test them experimentally in high throughput screens, leading to the discovery of a large number of new defense systems.
The reasons leading to the formation and maintenance of defense islands are still unclear. Makarova *et al.* :ref{doi=10.1128/JB.05535-11} observed a that defense islands often associated with mobile genetic elements, suggesting that defense systems travel through horizontal gene transfer, taking advantage of the MGEs' mobility. This observation in itself could explain the non-random localization of defense systems in the preferred "landing pads" (=*sinks*) of mobile genetic elements. Whether the colocalization of defense systems into these islands is purely due to there horizontal transmission, or whether they reflect a deeper functional implication such as coregulation and coordination, remains debated. The reasons leading to the formation and maintenance of defense islands are still unclear. Makarova *et al.* :ref{doi=10.1128/JB.05535-11} observed that defense islands are often associated with mobile genetic elements, suggesting that defense systems travel through horizontal gene transfer, taking advantage of the MGEs' mobility. This observation in itself could explain the non-random localization of defense systems in the preferred "landing pads" (=*sinks*) of mobile genetic elements. Whether the colocalization of defense systems into these islands is purely due to their horizontal transmission, or whether they reflect a deeper functional implication such as coregulation and coordination, remains debated.
...@@ -9,15 +9,15 @@ contributors: ...@@ -9,15 +9,15 @@ contributors:
## What are protein domains ? ## What are protein domains ?
Proteins can typically be decomposed into a set of structural or functional units called "domains" where each individual domain has a specific biological function (e.g. catalyzing a chemical reaction or binding to another protein). The combination of one or several protein domains within a protein determines its biological function. Proteins can typically be decomposed into a set of structural or functional units called "domains" where each domain has a specific biological function (e.g. catalyzing a chemical reaction or binding to another protein). The combination of one or several protein domains within a protein determines its biological function.
![illustration_thsa](/defensive_domain/ThsA.png){max-width=500px} ![illustration_thsa](/defensive_domain/ThsA.png){max-width=500px}
To examplify this idea, the figure is a depiction of the ThsA protein involved in the [Thoeris](/defense-systems/thoeris) defense system in *Bacillus cereus*. The protein is composed of two domains : a SIR2-like domain (blue) and a SLOG domain (green). The SLOG domain of ThsA is able to bind to cyclic Adenosine Diphosphate Ribose (cADPR), a signalling molecule produced by ThsB upon phage infection. Binding of cADPR activates the Nicotinamide Adenine Dinucleotide (NAD) depletion activity of the SIR2-like domain which causes abortive infection. This shows how the presence of two domains in this protein allows it to be activated by the sensor component of the system (ThsB) and to trigger the immune response mechanism :ref{doi=10.1038/s41586-021-04098-7}. To examplify this idea, the figure is a depiction of the ThsA protein involved in the [Thoeris](/defense-systems/thoeris) defense system in *Bacillus cereus*. The protein is composed of two domains: a SIR2-like domain (blue) and a SLOG domain (green). The SLOG domain of ThsA can bind to cyclic Adenosine Diphosphate Ribose (cADPR), a signalling molecule produced by ThsB upon phage infection. The binding of cADPR activates the Nicotinamide Adenine Dinucleotide (NAD) depletion activity of the SIR2-like domain which causes abortive infection. This shows how the presence of two domains in this protein allows it to be activated by the sensor component of the system (ThsB) and to trigger the immune response mechanism :ref{doi=10.1038/s41586-021-04098-7}.
## Domain characterization helps to understand the biological function of a protein ## Domain characterization helps to understand the biological function of a protein
Although a considerable diversity of molecular mechanisms have been described for defense systems, it is striking to observe that some functional domains are recurrently involved in antiphage defense :ref{doi=10.1038/s41586-021-04098-7}. When studying the presence of a new defense system, the *in silico* characterization of the domains present in the system can provide valuable information regarding the molecular mechanism of the system. If one protein of the system contains for example a TerB domain, this might indicate that the system is involved in membrane integrity surveillance as this domain was previously shown to be associated with the periplasmic membrane :ref{doi=10.1016/j.chom.2022.09.017}. If a protein of the system contains a TIR domain this might indicate that the system possess a NAD degradation activity or that the protein could multimerize as both functions have been shown for this domain in the past :ref{doi=10.3389/fimmu.2021.784484}. Although a considerable diversity of molecular mechanisms have been described for defense systems, it is striking to observe that some functional domains are recurrently involved in antiphage defense :ref{doi=10.1038/s41586-021-04098-7}. When studying the presence of a new defense system, the *in silico* characterization of the domains present in the system can provide valuable information regarding the molecular mechanism of the system. If one protein of the system contains for example a TerB domain, this might indicate that the system is involved in membrane integrity surveillance as this domain was previously shown to be associated with the periplasmic membrane :ref{doi=10.1016/j.chom.2022.09.017}. If a protein of the system contains a TIR domain this might indicate that the system possesses a NAD degradation activity or that the protein could multimerize as both functions have been shown for this domain in the past :ref{doi=10.3389/fimmu.2021.784484}.
## Domains can be conserved throughout evolution ## Domains can be conserved throughout evolution
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# Anti-defense systems: # Anti-defense systems:
This article is non-exhaustive but introduces the topic of an-defense systems. Several reviews mentioned here did a great in-depth characterization of the known anti-defense phage mechanism :ref{doi=10.3389/fmicb.2023.1211793,10.1016/j.jmb.2023.167974,10.1038/nrmicro3096}. This article is non-exhaustive but introduces the topic of anti-defense systems. Several reviews mentioned here did a great in-depth characterization of the known anti-defense phage mechanism :ref{doi=10.3389/fmicb.2023.1211793,10.1016/j.jmb.2023.167974,10.1038/nrmicro3096}.
Several strategies allow phages to avoid bacterial defenses to successfully complete an infectious cycle. In particular, anti-defense proteins are bacteriophage proteins that specifically act against a bacterial defense system, and thus allow bacteriophages to bypass the bacterial immune system. The most well-described category of anti-defense proteins are the anti-CRISPR proteins (Acr), that have been thoroughly reviewed previously :ref{doi=10.1038/nrmicro.2017.120,10.1016/j.jmb.2023.167974}. However, concomitant with the renewed interest of the field to identify new bacterial defense systems, many anti-defense proteins targeting diverse defense systems have recently been described. Using a non-exhaustive list of anti-defense proteins as examples, I will outline several general categories of anti-defense mechanism. However, I will not focus on another common phage anti-defense strategy that relies on modifying their components, such as mutating the proteins that trigger the defense to escape, or changing their DNA to avoid targeting by restriction-modification or CRISPR systems. Several strategies allow phages to avoid bacterial defenses to successfully complete an infectious cycle. In particular, anti-defense proteins are bacteriophage proteins that specifically act against a bacterial defense system and thus allow bacteriophages to bypass the bacterial immune system. The most well-described category of anti-defense proteins is the anti-CRISPR proteins (Acr), which have been thoroughly reviewed previously :ref{doi=10.1038/nrmicro.2017.120,10.1016/j.jmb.2023.167974}. However, concomitant with the renewed interest of the field to identify new bacterial defense systems, many anti-defense proteins targeting diverse defense systems have recently been described. Using a non-exhaustive list of anti-defense proteins as examples, I will outline several general categories of anti-defense mechanisms. However, I will not focus on another common phage anti-defense strategy that relies on modifying their components, such as mutating the proteins that trigger the defense to escape or changing their DNA to avoid targeting by restriction-modification or CRISPR systems.
Anti-defense proteins are crucial to understand the evolutionary arms race between bacteria and their phages, as they likely drive the diversification of bacterial defense systems. Some defense system even evolved to recognize anti-defense proteins as activators, providing multiple lines of defense during phage infection :ref{doi=10.1016/j.cell.2023.02.029}. Moreover, these proteins are also important to mediate phage/phage interactions. Indeed, anti CRISPR proteins were suggested to be involved in phage/phage collaboration, in which a primo-infection by a phage carrying an anti-CRISPR protein is unsuccessful but leaves the bacteria immunosuppressed and therefore sensitive to a second phage infection :ref{doi=10.1016/j.jmb.2023.167974}. Considering the importance of overcoming bacterial defenses for phages, it is likely that a significant part of the phage proteins of unknown function currently found in phage sequenced genomes act as anti-defense. Some anti-defense proteins were shown to colocalize in phage genomes, suggesting comparative genomics could be used to identify now anti-defense proteins, similar to what has been done very successfully for bacteria :ref{doi=10.1038/s41467-020-19415-3}. In general, recent studies have used a range of screening methods to identify new anti-defense proteins, and it is expected that many new anti-defense proteins will be described in the coming years. Anti-defense proteins are crucial to understand the evolutionary arms race between bacteria and their phages, as they likely drive the diversification of bacterial defense systems. Some defense systems even evolved to recognize anti-defense proteins as activators, providing multiple lines of defense during phage infection :ref{doi=10.1016/j.cell.2023.02.029}. Moreover, these proteins are also important in mediating phage/phage interactions. Indeed, anti-CRISPR proteins were suggested to be involved in phage/phage collaboration, in which a primo-infection by a phage carrying an anti-CRISPR protein is unsuccessful but leaves the bacteria immunosuppressed and therefore sensitive to a second phage infection :ref{doi=10.1016/j.jmb.2023.167974}. Considering the importance of overcoming bacterial defenses for phages, it is likely that a significant part of the phage proteins of unknown function currently found in phage-sequenced genomes act as anti-defense. Some anti-defense proteins were shown to colocalize in phage genomes, suggesting comparative genomics could be used to identify new anti-defense proteins, similar to what has been done very successfully for bacteria :ref{doi=10.1038/s41467-020-19415-3}. In general, recent studies have used a range of screening methods to identify new anti-defense proteins, and it is expected that many new anti-defense proteins will be described in the coming years.
## Anti-defense proteins target all stages of bacterial defenses ## Anti-defense proteins target all stages of bacterial defenses
Most anti-defense proteins described to date directly bind a bacterial defense protein to block its activity. However, several other strategies have been described such as post-translational modification of a target, spatial segregation or signaling molecule degradation :ref{doi=10.3389/fmicb.2023.1211793}. They have been described to target all stages of bacterial defense. Most anti-defense proteins described to date directly bind a bacterial defense protein to block its activity. However, several other strategies have been described such as post-translational modification of a target, spatial segregation or signaling molecule degradation :ref{doi=10.3389/fmicb.2023.1211793}. They have been described to target all stages of bacterial defense.
Bacterial defenses can be separated in two broad categories: external and internal defenses. Bacterial defenses can be separated into two broad categories: external and internal defenses.
### External defenses ### External defenses
...@@ -27,13 +27,13 @@ Bacteria can hide receptors behind surface structures such as extracellular poly ...@@ -27,13 +27,13 @@ Bacteria can hide receptors behind surface structures such as extracellular poly
Bacteria encode a variety of defense systems that prevent phage infection from progressing in various ways. Despite all this variability, all bacterial defense systems are schematically composed of three parts: a sensor recognizing the infection, an effector that achieves protection and a way to transmit the information between the sensor and the effector, either through signaling molecules or protein-protein interactions. Phage anti-defense proteins can target all three of these components. Bacteria encode a variety of defense systems that prevent phage infection from progressing in various ways. Despite all this variability, all bacterial defense systems are schematically composed of three parts: a sensor recognizing the infection, an effector that achieves protection and a way to transmit the information between the sensor and the effector, either through signaling molecules or protein-protein interactions. Phage anti-defense proteins can target all three of these components.
- Sensor targeting: - Sensor targeting:
- Competitive binding to the sensor: an anti-DSR2 protein from phages phi3T and SPbeta can bind the bacterial DSR2 protein and prevent the physical interaction between DSR2 and its phage activator, the tail tube protein :ref{doi=10.1038/s41564-022-01207-8}. Moreover, Ocr protein from T7 can mimic a B-form DNA oligo and acts as a competitive inhibitor of bacterial type I restriction modification systems :ref{doi=10.1016/s1097-2765(02)00435-5}. - Competitive binding to the sensor: an anti-DSR2 protein from phages phi3T and SPbeta can bind the bacterial DSR2 protein and prevent the physical interaction between DSR2 and its phage activator, the tail tube protein :ref{doi=10.1038/s41564-022-01207-8}. Moreover, Ocr protein from T7 can mimic a B-form DNA oligo and acts as a competitive inhibitor of bacterial type I restriction modification systems :ref{doi=10.1016/s1097-2765(02)00435-5}.
- Masking the activator: some jumbo phages are able to produce a nucleus-like proteinaceous structure that hides phage DNA and replication machinery away from DNA-targeted systems such as type I CRISPR system :ref{doi=10.1038/s41564-019-0612-5}. - Masking the activator: some jumbo phages can produce a nucleus-like proteinaceous structure that hides phage DNA and replication machinery away from DNA-targeted systems such as type I CRISPR system :ref{doi=10.1038/s41564-019-0612-5}.
- Transmission targeting: - Transmission targeting:
- Degradation of signaling molecules: many systems rely on the production of a nucleotidic signaling molecule after phage sensing to activate the effector such as Pycsar, CBASS, and Thoeris systems. Phages possess proteins that can degrade these molecules to prevent effector activation, such as the anti CBASS Acb1 from phage T4 and the anti Pycsar Apyc1 from phage SBSphiJ :ref{doi=10.1038/s41586-022-04716-y}. - Degradation of signaling molecules: many systems rely on the production of a nucleotidic signaling molecule after phage sensing to activate the effector such as Pycsar, CBASS, and Thoeris systems. Phages possess proteins that can degrade these molecules to prevent effector activation, such as the anti-CBASS Acb1 from phage T4 and the anti-Pycsar Apyc1 from phage SBSphiJ :ref{doi=10.1038/s41586-022-04716-y}.
- Sequestration of signaling molecules: an alternative strategy is to bind the signaling molecule very tightly without degrading it, which still prevents effector activation but is presumably easier to evolve than a catalysis-dependent degradation. These phage proteins are called sponges, and two were identified as anti-Thoeris: Tad1 from phage SBSphiJ7 and Tad2 from phage SPO1 and SPO1L3 :ref{doi=10.1038/s41586-022-05375-9,10.1038/s41586-023-06869-w}. - Sequestration of signaling molecules: an alternative strategy is to bind the signaling molecule very tightly without degrading it, which still prevents effector activation but is presumably easier to evolve than a catalysis-dependent degradation. These phage proteins are called sponges, and two were identified as anti-Thoeris: Tad1 from phage SBSphiJ7 and Tad2 from phage SPO1 and SPO1L3 :ref{doi=10.1038/s41586-022-05375-9,10.1038/s41586-023-06869-w}.
- Effector targeting: - Effector targeting:
- Direct binding to block activity: Multiple anti-CRISPR protein have been described that can directly bind all the different components of the Cas complex to prevent DNA degradation :ref{doi=10.3389/fmicb.2023.1211793,10.1146/annurev-genet-120417-031321}. So far, this is the most abundant category of anti-defense protein described, and it is not restricted to only anti-CRISPR proteins. - Direct binding to block activity: Multiple anti-CRISPR proteins have been described that can directly bind all the different components of the Cas complex to prevent DNA degradation :ref{doi=10.3389/fmicb.2023.1211793,10.1146/annurev-genet-120417-031321}. So far, this is the most abundant category of anti-defense protein described, and it is not restricted to only anti-CRISPR proteins.
- Antitoxin mimicking: toxin-antitoxin defense systems rely on a toxin effector and an antitoxin that will toxin-mediated toxicity in absence of phage infection. Phages can highjack this process by mimicking the antitoxin to prevent toxin activity even during infection. For instance, phage ϕTE can produce a short repetitive RNA that mimics the ToxI RNA antitoxin of type III toxin-antitoxin system ToxIN and evade defense mediated by this system :ref{doi=10.1371/journal.pgen.1003023}. - Antitoxin mimicking: toxin-antitoxin defense systems rely on a toxin effector and an antitoxin that will toxin-mediated toxicity in the absence of phage infection. Phages can hijack this process by mimicking the antitoxin to prevent toxin activity even during infection. For instance, phage ϕTE can produce a short repetitive RNA that mimics the ToxI RNA antitoxin of type III toxin-antitoxin system ToxIN and evades defense mediated by this system :ref{doi=10.1371/journal.pgen.1003023}.
...@@ -25,7 +25,7 @@ AbiA is one of the so-called "Abi" systems for "Abortive infection" discovered i ...@@ -25,7 +25,7 @@ AbiA is one of the so-called "Abi" systems for "Abortive infection" discovered i
Since it was discovered a similarity in amino acids was found with [AbiK](/defense-systems/abik). Since it was discovered a similarity in amino acids was found with [AbiK](/defense-systems/abik).
However, with the discovery of dozens of new systems, it was categorized as one of the UG/Abi defense systems :ref{doi=10.1093/nar/gkac467} along with [DRT](/defense-systems/drt) different subsystems, [Abik](/defense-systems/abik), [AbiP2](/defense-systems/abip2) and [Rst_RT_Nitralase_TM](/defense-systems/rst_rt-nitrilase-tm). However, with the discovery of dozens of new systems, it was categorized as one of the UG/Abi defense systems :ref{doi=10.1093/nar/gkac467} along with [DRT](/defense-systems/drt) different subsystems, [AbiK](/defense-systems/abik), [AbiP2](/defense-systems/abip2) and [Rst_RT_Nitralase_TM](/defense-systems/rst_rt-nitrilase-tm).
Those systems are characterized by the presence of a reverse transcriptase domain of the "Unknown Group RT". Those systems are characterized by the presence of a reverse transcriptase domain of the "Unknown Group RT".
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...@@ -24,7 +24,7 @@ relevantAbstracts: ...@@ -24,7 +24,7 @@ relevantAbstracts:
AbiB is a single-protein abortive infection defense system from *Lactococcus* that degrades mRNA. AbiB is a single-protein abortive infection defense system from *Lactococcus* that degrades mRNA.
## Molecular mechanism ## Molecular mechanism
AbiB system is still poorly understood. It is a single-protein system that was described as an abortive infection system. Upon phage infection, AbiB activation leads to a strong degradation of mRNAs :ref{doi=10.1046/j.1365-2958.1996.371896.x} that is expected to be the mechanism of phage inhibition. AbiB expression is constitutive and does increase during phage infection. It is only activated during phage infection, most likely through the recognition of an early phage protein. Which protein, and whether this activation is direct or indirect remains to be elucidated. AbiB system is still poorly understood. It is a single-protein system that was described as an abortive infection system. Upon phage infection, AbiB activation leads to a strong degradation of mRNAs :ref{doi=10.1046/j.1365-2958.1996.371896.x} which is expected to be the mechanism of phage inhibition. AbiB expression is constitutive and does increase during phage infection. It is only activated during phage infection, most likely through the recognition of an early phage protein. Which protein, and whether this activation is direct or indirect remains to be elucidated.
## Example of genomic structure ## Example of genomic structure
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...@@ -23,7 +23,7 @@ relevantAbstracts: ...@@ -23,7 +23,7 @@ relevantAbstracts:
## Description ## Description
AbiD is a single gene system system discovered in May 1995 in the plasmid pBF61 of *Lactococcus lactis* :ref{doi=10.1128/aem.61.5.2023-2026.1995}. An homolog of AbiD, named AbiD1 was discovered in July 1995 :ref{doi=10.1128/jb.177.13.3818-3823.1995}. AbiD is a single gene system discovered in May 1995 in the plasmid pBF61 of *Lactococcus lactis* :ref{doi=10.1128/aem.61.5.2023-2026.1995}. An homolog of AbiD, named AbiD1 was discovered in July 1995 :ref{doi=10.1128/jb.177.13.3818-3823.1995}.
AbiD is one of the so-called "Abi" systems for "Abortive infection" discovered in the 90's in research related to the dairy industry :ref{doi=10.1016/j.mib.2005.06.006}. AbiR is classified as a possible abortive infection in :ref{doi=10.1016/j.mib.2023.102312}. AbiD is one of the so-called "Abi" systems for "Abortive infection" discovered in the 90's in research related to the dairy industry :ref{doi=10.1016/j.mib.2005.06.006}. AbiR is classified as a possible abortive infection in :ref{doi=10.1016/j.mib.2023.102312}.
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...@@ -26,7 +26,7 @@ AbiL was discovered in Lactococcus lactis. A plasmid containing the defense syst ...@@ -26,7 +26,7 @@ AbiL was discovered in Lactococcus lactis. A plasmid containing the defense syst
## Molecular mechanism ## Molecular mechanism
Abortive infection. the PF13707 domain includes the RloB protein that is found within a bacterial restriction modification operon. This family includes the AbiLii protein that is found as part of a plasmid encoded phage abortive infection mechanism. Deletion within abiLii abolished the phage resistance. The family includes some proteins annotated as CRISPR Csm2 proteins. Abortive infection. the PF13707 domain includes the RloB protein that is found within a bacterial restriction-modification operon. This family includes the AbiLii protein that is found as part of a plasmid-encoded phage abortive infection mechanism. Deletion within abiLii abolished the phage resistance. The family includes some proteins annotated as CRISPR Csm2 proteins.
## Example of genomic structure ## Example of genomic structure
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...@@ -27,7 +27,7 @@ AbiR is one of the so-called "Abi" systems for "Abortive infection" discovered i ...@@ -27,7 +27,7 @@ AbiR is one of the so-called "Abi" systems for "Abortive infection" discovered i
AbiR is composed of 3 genes: AbiRa, AbiRb, AbiRc. AbiR is composed of 3 genes: AbiRa, AbiRb, AbiRc.
AbiRa encodes a sigma70 RNA polymerase subunit. AbiRb as homology with ParB nuclease domain according to HHpred. AbiRa encodes a sigma70 RNA polymerase subunit. AbiRb as homology with ParB nuclease domain according to HHpred.
AbiRc has two different domains: a N_terminal PLD domain (PF13091) and at the C term an SNF2 DNA dependant ATPase. AbiRc has two different domains: an N_terminal PLD domain (PF13091) and at the C term an SNF2 DNA-dependent ATPase.
## Molecular mechanism ## Molecular mechanism
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...@@ -24,7 +24,7 @@ relevantAbstracts: ...@@ -24,7 +24,7 @@ relevantAbstracts:
AbiU is a single-protein abortive infection defense system described in *Lactococcus*. AbiU is a single-protein abortive infection defense system described in *Lactococcus*.
## Molecular mechanism ## Molecular mechanism
The molecular mechanism of AbiU is not well understood. It was shown that cells expressing AbiU showed delayed transcription of phage DNA, although how it is achieved, or how does it protect the bacterial culture is not understood. AbiU was shown to be encoded near another gene that seems to be an inhibitor of defense :ref{doi=10.1128/AEM.67.11.5225-5232.2001}. The molecular mechanism of AbiU is not well understood. It was shown that cells expressing AbiU showed delayed transcription of phage DNA, although how it is achieved, or how it protects the bacterial culture is not understood. AbiU was shown to be encoded near another gene that seems to be an inhibitor of defense :ref{doi=10.1128/AEM.67.11.5225-5232.2001}.
## Example of genomic structure ## Example of genomic structure
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...@@ -20,7 +20,7 @@ relevantAbstracts: ...@@ -20,7 +20,7 @@ relevantAbstracts:
## Description ## Description
Aditi was discovered among other systems in 2022 :ref{doi=10.1016/j.chom.2022.09.017}. Aditi was discovered among other systems in 2022 :ref{doi=10.1016/j.chom.2022.09.017}.
Aditi is composed of two genes: DitA, DitB. Both are of unknown function, and have no homology to any known domain. Aditi is composed of two genes: DitA, DitB. Both are of unknown function and have no homology to any known domain.
Aditi is named after the Hindu guardian goddess of all life. Aditi is named after the Hindu guardian goddess of all life.
## Molecular mechanisms ## Molecular mechanisms
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...@@ -39,9 +39,9 @@ Avs systems sometimes include additional essential small genes on top of the can ...@@ -39,9 +39,9 @@ Avs systems sometimes include additional essential small genes on top of the can
## Example of genomic structure ## Example of genomic structure
The Avs system have been describe in a total of 5 subsystems (in the old classification). The Avs system has been described in a total of 5 subsystems (in the old classification).
Here is some examples found in the RefSeq database: Here are some examples found in the RefSeq database:
![avs_i](/avs/Avs_I.svg){max-width=750px} ![avs_i](/avs/Avs_I.svg){max-width=750px}
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...@@ -22,10 +22,10 @@ relevantAbstracts: ...@@ -22,10 +22,10 @@ relevantAbstracts:
# Borvo # Borvo
## Description ## Description
Borvo is a single-gene anti-phage system that was identify through bioinformatic prediction and experimental validation :ref{doi=10.1016/j.chom.2022.09.017}. Borvo is a single-gene anti-phage system that was identified through bioinformatic prediction and experimental validation :ref{doi=10.1016/j.chom.2022.09.017}.
## Molecular mechanisms ## Molecular mechanisms
Mutations in the phage DNA polymerase can allow phages to escape Borvo defense, indicating that it could be the trigger of the system :ref{doi=10.1016/j.cell.2023.02.029}. Borvo is a suspected abortive infection :ref{doi=10.1016/j.cell.2023.02.029}. However as far as we are aware, the precise molecular mechanism of Borvo is unknown. Mutations in the phage DNA polymerase can allow phages to escape Borvo defense, indicating that it could be the trigger of the system :ref{doi=10.1016/j.cell.2023.02.029}. Borvo is a suspected abortive infection :ref{doi=10.1016/j.cell.2023.02.029}. However, as far as we are aware, the precise molecular mechanism of Borvo is unknown.
## Example of genomic structure ## Example of genomic structure
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...@@ -27,7 +27,7 @@ Interestingly, part of the BstA locus appears to encode an anti-BstA genetic ele ...@@ -27,7 +27,7 @@ Interestingly, part of the BstA locus appears to encode an anti-BstA genetic ele
## Molecular mechanism ## Molecular mechanism
The defense mechanism encoded by BstA remains to be elucidated. Experimental observation suggest that BtsA could act through an abortive infection mechanism. Fluorescence microscopy experiments suggest that the BstA protein colocalizes with phage DNA. The BstA protein appears to inhibit phage DNA replication during lytic phage infection cycles :ref{doi=10.1016/j.chom.2021.09.002}. The defense mechanism encoded by BstA remains to be elucidated. Experimental observation suggests that BtsA could act through an abortive infection mechanism. Fluorescence microscopy experiments suggest that the BstA protein colocalizes with phage DNA. The BstA protein appears to inhibit phage DNA replication during lytic phage infection cycles :ref{doi=10.1016/j.chom.2021.09.002}.
## Example of genomic structure ## Example of genomic structure
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