components/content/StructureDb.vue

@@ -5,7 +5,7 @@ import type { SortItem } from "@/components/ServerDbTable.vue"
 import { ServerDbTable } from "#components"
 const sortBy: Ref<SortItem[]> = ref([{ key: 'system', order: "asc" }])
 const itemValue = ref("id");
-const facets: Ref<string[]> = ref(["system", "completed", "prediction_type", ])
+const facets: Ref<string[]> = ref(["system", "completed", "prediction_type",])
 const headers: Ref<Object[]> = ref([
     { title: 'Structure', key: 'structure', sortable: false, removable: false },
     { title: "Type", key: "system", removable: false },
@@ -56,7 +56,8 @@ function pdbNameToCif(pdbPath: string) {
 
 
 function toSystemName(rawName: string) {
-    return rawName.split(/_|-0/)[0].toLocaleLowerCase()
+    // split on __ in system_genes
+    return rawName.split("__")[0].toLocaleLowerCase()   
 
 }
 
@@ -93,7 +94,7 @@ function remove(key) {
         </template>
         <template #[`item.structure`]="{ item }">
             <MolstarPdbePlugin v-if="item?.pdb && item.pdb !== 'na'"
-                :data-urls="[`/${toSystemName(item.system)}/${pdbNameToCif(item.pdb)}`]" uniq>
+                :data-urls="[`/${toSystemName(item.system_genes)}/${pdbNameToCif(item.pdb)}`]" uniq>
             </MolstarPdbePlugin>
             <span v-else class="d-flex flex-wrap align-center justify-center">
                 <v-icon color="warning" icon="md:dangerous"></v-icon>

content/2.general-concepts/5.defense-systems-discovery.md

@@ -2,6 +2,15 @@
 title: Discovery of defense systems
 layout: article
 toc: true
+contributors:
+  - Helena Shomar
 ---
 
-Defense systems are known since the birth of molecular biology. Then, more were discovered.
+# Discovery of defense systems
+
+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.
+
+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.
+

content/2.general-concepts/7.mge-defense-systems.md

 ---
 title: Defense Systems and MGE
-layout: article-no-toc
+contributors: 
+    - Marian Dominguez-Mirazo
+layout: article
 ---
 
-Defense systems help bacteria against mobile genetic elements (MGE), such as phage or plasmids.
-Yet, some defense systems favor certain MGE, or some MGE carry defense systems.
\ No newline at end of file
+Mobile genetic elements (MGEs), such as plasmids, bacteriophages, and phage satellites, facilitate horizontal gene transfer (HGT) within microbial populations, playing a crucial role in the genetic diversity and genomic evolution of bacteria :ref{doi=10.1098/rstb.2020.0460}. These elements expedite the exchange of genetic material among bacterial cells, promoting the dissemination of advantageous traits like antibiotic resistance, virulence factors, and metabolic capabilities, allowing bacteria to adapt to dynamic environments :ref{doi=10.1098/rstb.2020.0460}. However, the presence of MGEs can impose a substantial fitness cost on the bacterial host, as in the case of lytic phage infections. To counteract parasitic genomic elements, including viruses and other MGEs, bacteria have evolved defense systems. These defense systems are often disadvantageous under low parasite pressure, leading to their occasional loss. However, as the pressure from parasites increases, these defense systems become advantageous. Consequently, defense systems in bacteria exhibit high mobility and transfer rates :ref{doi=10.1038/s41576-019-0172-9}. Interestingly, a large fraction of defense systems in bacteria are encoded by MGEs :ref{doi=10.1038/s41467-022-30269-9,10.1371/journal.pbio.3001514}. While sometimes the fitness interests of MGEs and the bacterial host are aligned, these systems are likely to be selected because they benefit the MGE encoding it rather than the host cell who :ref{doi=10.1371/journal.pbio.3001514,10.1038/s41576-019-0172-9}. This benefit may include preventing other mobile elements from infecting the same cell and competing for essential resources. The presence of defense systems can, in turn, have an effect in gene flow who :ref{doi=10.1371/journal.pbio.3001514}. 

content/3.defense-systems/abih.md

@@ -18,6 +18,13 @@ relevantAbstracts:
 ---
 
 # AbiH
+
+## Description
+AbiH is a single-gene abortive infection system described in Lactococcus.
+
+## Molecular mechanism 
+To the best of our knowledge, no molecular mechanism has been described so far for AbiH.
+
 ## Example of genomic structure
 
 The AbiH is composed of 1 protein: AbiH.

content/3.defense-systems/card_nlr.md

@@ -6,12 +6,22 @@ tableColumns:
       doi: 10.1101/2023.05.28.542683
       abstract: |
         Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Upon pathogen recognition by NLR proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore forming proteins to and induce pyroptotic cell death. Here we show that CARD-like domains are present in defense systems that protect bacteria against phage. The bacterial CARD is essential for protease-mediated activation of certain bacterial gasdermins, which promote cell death once phage infection is recognized. We further show that multiple anti-phage defense systems utilize CARD-like domains to activate a variety of cell death effectors. We find that these systems are triggered by a conserved immune evasion protein that phages use to overcome the bacterial defense system RexAB, demonstrating that phage proteins inhibiting one defense system can activate another. We also detect a phage protein with a predicted CARD-like structure that can inhibit the CARD-containing bacterial gasdermin system. Our results suggest that CARD domains represent an ancient component of innate immune systems conserved from bacteria to humans, and that CARD-dependent activation of gasdermins is conserved in organisms across the tree of life.
+    Sensor: Unknown
+    Activator: Unknown
+    Effector: Membrane disrupting or other
     PFAM: PF00082, PF00089, PF00614, PF01223, PF13091, PF13191, PF13365
+contributors:
+    - Marian Dominguez-Mirazo
+relevantAbstract:
+    - doi: 10.1101/2023.05.28.542683
 ---
 
 # CARD_NLR
+## Description
+Pore-forming proteins called gasdermins control cell-death response to infection in animals. Gasdermins are also present in bacteria where they have been shown to act as an abortive infection system that permeabilizes the cell membrane before phage release :ref{doi=10.1126/science.abj8432,10.1101/2023.05.28.542683}. In *Lysobacter*, the gasdermin operon includes two genes encoding trypsin-like protease domains, and a gene encoding an ATPase domain :ref{doi=10.1101/2023.05.28.542683}. Intact active sites for the second protease and the ATPase, but not the first protease, are required for succesful phage defense :ref{doi=10.1126/science.abj8432}. The domain architecture of the ATPase suggests it belongs to a protein family that is considered the ancestor of the eukaryotic  nucleotide oligomerization domain (NOD)-like receptor (NLR) protein family :ref{doi=10.1101/2023.05.28.542683}. In animals, NLR initiates the formation of the inflammasome complex :ref{doi=10.1126/science.abe3069}. The second protease contains a region with similar structure to human CARD domain :ref{doi=10.1101/2023.05.28.542683}. The CARD domain takes part on the assembly of immune protein complexes :ref{doi=10.1038/sj.cdd.4401890}. The CARD-like domain in the *Lysobacter* system is required for succesful phage defense :ref{doi=10.1101/2023.05.28.542683}. Homology searches recovered multiple bacterial operons that include two proteases, one of them containing a CARD-like domain, and a NLR-like protein. In most cases, the effector gasdermin gene was replaced by another gene:ref{doi=10.1101/2023.05.28.542683}. The operon found in *Pedobacter rhizosphaerae* exhibits phage defense capabilities and contains a protein with phospholipase and endonuclease domains replacing the gasdermin gene. This system confers protection against the same phages as the *Lysobacter* gasdermin containing system, suggesting that the proteases and ATPase participate in phage specificity and recognition. 
 
-## To do 
+## Molecular mechanisms
+For the *Lysobacter* system, the effector has been described as a pore-formin protein that disrupts the cell membrane :ref{doi=10.1101/2023.05.28.542683}. To our knowledge, other parts of the molecular mechanisms have yet to be elucidated. 
 
 ## Example of genomic structure
 
@@ -49,13 +59,3 @@ The system was detected in 57 different species.
 
 Proportion of genome encoding the CARD_NLR system for the 14 phyla with more than 50 genomes in the RefSeq database.
 
-
-## Relevant abstract
-::relevant-abstracts
----
-items:
-    - doi: 10.1101/2023.05.28.542683
-
----
-::
-

content/3.defense-systems/drt.md

@@ -10,9 +10,37 @@ tableColumns:
     Activator: Unknown
     Effector: Unknown
     PFAM: PF00078
+contributors: 
+  - Helena Shomar
+  - Marie Guillaume
+relevantAbstracts:
+  - doi: 10.1093/nar/gkac467
+  - doi: 10.1126/science.aba0372
 ---
 
 # DRT
+
+## Description
+DRT stands for Defense-associated Reverse Transcriptases.
+DRTs are a widespread and highly diverse family of defense systems, characterized by reverse transcriptase (RTs) components with antiphage properties. These RTs belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs.
+
+DRT systems were experimentally validated in _Escherichia coli_ and demonstrated to be effective against an array of diverse phages.
+So far, DRTs have been classified in 9 different types. Essential components of each DRT type are:
+- DRT Type 1:   UG1  (RT-nitrilaseTM domains)
+- DRT Type 2:   UG2  (RT domain)
+- DRT Type 3:   UG3  (RT domain), UG8 (RT domain) and ncRNA
+- DRT Type 4:   UG15 (RT-alphaRep domains)
+- DRT Type 5:   UG16 (RT domain)
+- DRT Type 6:   UG12 (RT-alphaRep domains)
+- DRT Type 7:   UG10 (PrimS-RT-alphaRep domains)
+- DRT Type 8:   UG7  (RT-alphaRep-PDDExK domains)
+- DRT Type 9:   UG28 (RT-alphaRep domains) and ncRNA
+
+
+## Molecular mechanism
+To our knowledge, the molecular mechanism is unknown. 
+Similarly, for the other systems of this family, the molecular mechanism remain unknown. 
+
 ## Example of genomic structure
 
 A total of 9 subsystems have been described for the DRT system.
@@ -187,7 +215,7 @@ Escherichia coli
     Origin_3[ RT UG15 Type 4
 Escherichia coli 
 <a href='https://ncbi.nlm.nih.gov/protein/GCK53192.1'>GCK53192.1</a>] --> Expressed_3[Escherichia coli]
-    Expressed_3[Escherichia coli] ----> T5 & T3 & T7 & Phi-V1 & ZL19
+    Expressed_3[Escherichia coli] ----> T5 & T3 & T7 & Phi-V1 & ZL-19
     Gao_2020[<a href='https://doi.org/10.1126/science.aba0372'>Gao et al., 2020</a>] --> Origin_4
     Origin_4[ RT UG16 Type 5
 Escherichia coli  
@@ -251,12 +279,12 @@ end
         T3
         T7
         Phi-V1
-        ZL19
+        ZL-19
         T5
         T3
         T7
         Phi-V1
-        ZL19
+        ZL-19
         T2
         T2
         T5
@@ -272,14 +300,5 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
-    - doi: 10.1093/nar/gkac467
-    - doi: 10.1126/science.aba0372
 
----
-::
 

content/3.defense-systems/fs_hp.md

@@ -6,11 +6,21 @@ tableColumns:
       doi: 10.1016/j.cell.2022.07.014
       abstract: |
         Bacteria encode sophisticated anti-phage systems that are diverse and versatile and display high genetic mobility. How this variability and mobility occurs remains largely unknown. Here, we demonstrate that a widespread family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs), carry an impressive arsenal of defense mechanisms, which can be disseminated intra- and inter-generically by helper phages. These defense systems provide broad immunity, blocking not only phage reproduction, but also plasmid and non-cognate PICI transfer. Our results demonstrate that phages can mobilize PICI-encoded immunity systems to use them against other mobile genetic elements, which compete with the phages for the same bacterial hosts. Therefore, despite the cost, mobilization of PICIs may be beneficial for phages, PICIs, and bacteria in nature. Our results suggest that PICIs are important players controlling horizontal gene transfer and that PICIs and phages establish mutualistic interactions that drive bacterial ecology and evolution.
+    Sensor: Unknown
+    Activator: Unknown
+    Effector: Unknown
+contributors:
+    - Marian Dominguez-Mirazo
+relevantAbstracts:
+    - doi: 10.1016/j.cell.2022.07.014
 ---
 
 # FS_HP
 
-## To do 
+## Description
+PICIs (Phage-inducible chromosomal islands) are highly mobile genetic elements that reside in the bacterial chromosome in the absence of a helper phage. Following infection by the helper phage, PICIs excise and replicate by hijacking the helper phage machinery. The FS_HP system was discovered in E. fergusonii through manual search for immune systems in flanking regions of gram-negative PICIs :ref{doi=10.1016/j.cell.2022.07.014}. It is composed by a single protein with a hypothetical domain, from which it derives the HP part of its name. The system showcases a broad defense spectrum. It was tested against 15 lytic phages in 3 gram negative bacteria, and protected the bacterial host against 3 unrelated phages in 2 different bacteria species. FS_HP also blocked the formation of phage particles upon induction of the P22 S. enterica prophage. Therefore, the system can block phage in both lytic and lysogenic life cycles. It was also shown to reduce the production of transducing particles. 
+## Molecular mechanisms
+As far as we are aware, the molecular mechanism is unknown. 
 
 ## Example of genomic structure
 
@@ -76,11 +86,3 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstract
-::relevant-abstracts
----
-items:
-    - doi: 10.1016/j.cell.2022.07.014
-
----
-::

content/3.defense-systems/gao_mza.md

@@ -10,9 +10,20 @@ tableColumns:
     Activator: Unknown
     Effector: Unknown
     PFAM: PF00023, PF04542, PF04545, PF10592, PF10593, PF13589, PF13606, PF14390
+contributors:
+    - Hugo Vaysset
+relevantAbstracts:
+    - doi: 10.1126/science.aba0372
 ---
 
 # Gao_Mza
+
+## Description
+Mza (MutL, Z1, DUF, AIPR) is a defense system composed of five proteins. Its antiphage activity was assessed by heterologous expression in *E. coli* against phages T2, T4, T5, lambda and M13 (ssDNA phage) :ref{doi=10.1126/science.aba0372}.  
+
+## Molecular mechanism
+As far as we are aware, the molecular mechanism is unknown. 
+
 ## Example of genomic structure
 
 The Gao_Mza is composed of 5 proteins: MzaA, MzaB, MzaC, MzaD and MzaE.
@@ -103,13 +114,4 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
-    - doi: 10.1126/science.aba0372
-
----
-::
 

content/3.defense-systems/gaps1.md

@@ -6,11 +6,23 @@ tableColumns:
       doi: 10.1101/2023.03.28.534373
       abstract: |
         Bacteria are found in ongoing conflicts with rivals and predators, which lead to an evolutionary arms race and the development of innate and adaptive immune systems. Although diverse bacterial immunity mechanisms have been recently identified, many remain unknown, and their dissemination within bacterial populations is poorly understood. Here, we describe a widespread genetic element, defined by the Gamma-Mobile-Trio (GMT) proteins, that serves as a mobile bacterial weapons armory. We show that GMT islands have cargo comprising various combinations of secreted antibacterial toxins, anti-phage defense systems, and secreted anti-eukaryotic toxins. This finding led us to identify four new anti-phage defense systems encoded within GMT islands and reveal their active domains and mechanisms of action. We also find the phage protein that triggers the activation of one of these systems. Thus, we can identify novel toxins and defense systems by investigating proteins of unknown function encoded within GMT islands. Our findings imply that the concept of "defense islands" may be broadened to include other types of bacterial innate immunity mechanisms, such as antibacterial and anti-eukaryotic toxins that appear to stockpile with anti-phage defense systems within GMT weapon islands.
+    Sensor: Phage-protein sensing
+    Activator: Unknown
+    Effector: Unknown
+contributors:
+    - Marian Dominguez-Mirazo
+relevantAbstracts:
+    - doi: 10.1101/2023.03.28.534373
 ---
 
 # GAPS1
 
-## To do 
+## Description
+The GAPS1 system is composed of a single protein. It was found in Gamma-Mobile-Trio (GMT) protein containing genomic island in *Vibrio*, and cloned into *E. coli* K-12 :ref{doi=10.1101/2023.03.28.534373}. The name GAPS derives from the "GMT-encoded Anti-Phage System" acronym. GAPS1 contains a predicted nuclease domain whose mutation prevents defense activity, however DNA degradation was not detected in targeted phage :ref{doi=10.1101/2023.03.28.534373}. Mutations in the folded capsid protein (Gp10) of phage T7 result in a escape phenotype, with GAPS1 shown to be activated upon Gp10 expression, suggesting activation of the system at late stages of the infection cycle :ref{doi=10.1101/2023.03.28.534373}. 
+
+## Molecular mechanisms
+The molecular mechanism remains to be fully elucidated. 
+
 
 ## Example of genomic structure
 
@@ -69,11 +81,4 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstract
-::relevant-abstracts
----
-items:
-    - doi: 10.1101/2023.03.28.534373
 
----
-::

content/3.defense-systems/lamassu-fam.md

@@ -9,21 +9,32 @@ tableColumns:
     Sensor: Unknown
     Activator: Unknown
     Effector: Diverse (Nucleic acid degrading (?), Nucleotide modifying (?), Membrane disrupting (?))
-    PFAM: PF00753, PF02463, PF05057, PF12532, PF13175, PF13289, PF13476, PF14130
+    PFAM: PF00753, PF02463, PF05057, PF12532, PF13175, PF13289, PF13476, PF14130  
+contributors: 
+    - Matthieu Haudiquet
+    - Aude Bernheim
+relevantAbstracts:
+    - doi: 10.1126/science.aar4120
+    - doi: 10.1016/j.chom.2022.09.017
+    - doi: 10.1093/nar/gkab883
+    - doi: 10.1038/s41586-022-04546-y 
+    - doi: 10.1101/2022.11.18.517080 
 ---
 
 # Lamassu-Fam
 ## Description
 
-The original types of Lamassu systems are Lamassu Type 1 and 2. They both necessarily comprise two genes *lmuA* and *lmuB*, to which a third gene (*lmuC*) is added in the case of Lamassu Type 2.  
+The original types of Lamassu systems are Lamassu Type 1 :ref{doi=10.1126/science.aar4120} and Type 2 :ref{doi=10.1016/j.chom.2022.09.017}. They both necessarily comprise two genes *lmuA* and *lmuB*, to which a third gene (*lmuC*) is added in the case of Lamassu Type 2.  
 
-More recently, Lamassu has been suggested to be a large family of defense systems, that can be classified into multiple subtypes. 
+Lamassu has been suggested to be a large family of defense systems, that can be classified into multiple subtypes :ref{doi=10.1016/j.chom.2022.09.017}. 
 
-These systems all encode the *lmuB* gene, and in most cases also comprise *lmuC.* In addition to these two core genes, Lamassu systems of various subtypes encode a third protein, hypothesized to be the Abi effector protein (3). This effector  can not only be LmuA (Lamassu Type1 and 2) but also proteins encoding endonuclease domains, SIR2-domains, or even hydrolase domains (3). Systems of the extended Lamassu-family can be found in 10% of prokaryotic genomes (3).
+These systems all encode the *lmuB* gene, and in most cases also comprise *lmuC*. In addition to these two core genes, Lamassu systems of various subtypes encode a third protein, hypothesized to be the Abi effector protein :ref{doi=10.1101/2022.05.11.491447}. This effector  can be proteins encoding endonuclease domains, SIR2-domains, or even hydrolase domains :ref{doi=10.1016/j.chom.2022.09.017}. Systems of the extended Lamassu-family can be found in 10% of prokaryotic genomes :ref{doi=10.1016/j.chom.2022.09.017}.
+
+Lamassu were also described as DdmABC in *Vibrio cholerae* :ref{doi=10.1038/s41586-022-04546-y,10.1101/2022.11.18.517080}. They were found to be antiplasmids and thus to eliminate plasmids from seventh pandemic *Vibrio cholerae* :ref{doi=10.1038/s41586-022-04546-y}.
 
 ## Molecular mechanism
 
-Lamassu systems function through abortive infection (Abi), but their molecular mechanism remains to be described.
+Lamassu systems function through abortive infection (Abi), but the molecular mechanism remains to be described. It was shown that, in Vibrio cholerae palindromic DNA sequences that are predicted to form stem-loop hairpin trigger the system :ref{doi=10.1101/2022.11.18.517080}. 
 
 ## Example of genomic structure
 
@@ -426,24 +437,3 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
-    - doi: 10.1016/j.chom.2022.09.017
-    - doi: 10.1038/s41586-022-04546-y
-    - doi: 10.1126/science.aar4120
-
----
-::
-
-
-## References
-
-1. Doron S, Melamed S, Ofir G, et al. Systematic discovery of antiphage defense systems in the microbial pangenome. *Science*. 2018;359(6379):eaar4120. doi:10.1126/science.aar4120
-
-2. Payne LJ, Todeschini TC, Wu Y, et al. Identification and classification of antiviral defence systems in bacteria and archaea with PADLOC reveals new system types. *Nucleic Acids Res*. 2021;49(19):10868-10878. doi:10.1093/nar/gkab883
-
-3. Millman, A., Melamed, S., Leavitt, A., Doron, S., Bernheim, A., Hör, J., Lopatina, A., Ofir, G., Hochhauser, D., Stokar-Avihail, A., Tal, N., Sharir, S., Voichek, M., Erez, Z., Ferrer, J.L.M., Dar, D., Kacen, A., Amitai, G., Sorek, R., 2022. An expanding arsenal of immune systems that protect bacteria from phages. bioRxiv. https://doi.org/10.1101/2022.05.11.491447
-

content/3.defense-systems/lit.md

@@ -3,16 +3,33 @@ title: Lit
 layout: article
 tableColumns:
     article:
-      doi: 10.1186/1743-422X-7-360
+      doi: 10.1073/pnas.91.2.802
       abstract: |
-        Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC) and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit); and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes) of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context.
+        Bacteriophage T4 multiples poorly in Escherichia coli strains carrying the defective prophage, e14; the e14 prophage contains the lit gene for late inhibitor of T4 in E. coli. The exclusion is caused by the interaction of the e14-encoded protein, Lit, with a short RNA or polypeptide sequence encoded by gol from within the major head protein gene of T4. The interaction between Lit and the gol product causes a severe inhibition of all translation and prevents the transcription of genes downstream of the gol site in the same transcription unit. However, it does not inhibit most transcription, nor does it inhibit replication or affect intracellular levels of ATP. Here we show that the interaction of gol with Lit causes the cleavage of translation elongation factor Tu (EF-Tu) in a region highly conserved from bacteria to humans. The depletion of EF-Tu is at least partly responsible for the inhibition of translation and the phage exclusion. The only other phage-exclusion system to be understood in any detail also attacks a highly conserved cellular component, suggesting that phage-exclusion systems may yield important reagents for studying cellular processes.
     Sensor: Monitoring host integrity
     Activator: Direct
     Effector: Other (Cleaves an elongation factor, inhibiting cellular translation
     PFAM: PF10463
+contributors: 
+  - Lucas Paoli
+relevantAbstracts:
+  - doi: 10.1128/jb.169.3.1232-1238.1987
+  - doi: 10.1128/jb.170.5.2056-2062.1988
+  - doi: 10.1073/pnas.91.2.802
+  - doi: 10.1074/jbc.M002546200
+  - doi: 10.1186/1743-422X-7-360
 ---
 
 # Lit
+
+## Description
+
+Lit was first identified in 1989 :ref{doi=10.1128/jb.169.3.1232-1238.1987}, stands for late inhibitors of T4, and was found to inhibit phage T4 in Escherichia coli (K12). The Lit gene is found in the e14 cryptic prophage :ref{doi=10.1128/jb.170.5.2056-2062.1988}. Lit is also partially active against other T-even phages :ref{doi=10.1073/pnas.91.2.802}.
+
+## Molecular mechanisms
+
+The Lit system detects cleaves EF-Tu translation factor :ref{doi=10.1073/pnas.91.2.802} at a late stage of phage maturation, when the major capsid protein binds to EF-Tu and triggers its cleavage by Lit :ref{doi=10.1074/jbc.M002546200}. As a result, the translation is inhbited, which ultimately leads to cell death. Lit is part of the abortive infection category of defense systems.
+
 ## Example of genomic structure
 
 The Lit is composed of 1 protein: Lit.
@@ -69,15 +86,3 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
-    - doi: 10.1073/pnas.91.2.802
-    - doi: 10.1074/jbc.M002546200
-    - doi: 10.1186/1743-422X-7-360
-
----
-::
-

content/3.defense-systems/mmb_gp29_gp30.md

@@ -6,11 +6,19 @@ tableColumns:
       doi: 10.1038/nmicrobiol.2016.251
       abstract: |
         Temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses that infect mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that are either closely related (homotypic defence) or unrelated (heterotypic defence) to the prophage. Target specificity is unpredictable, ranging from a single target phage to one-third of those tested. The defence systems include a single-subunit restriction system, a heterotypic exclusion system and a predicted (p)ppGpp synthetase, which blocks lytic phage growth, promotes bacterial survival and enables efficient lysogeny. The predicted (p)ppGpp synthetase coded by the Phrann prophage defends against phage Tweety infection, but Tweety codes for a tetrapeptide repeat protein, gp54, which acts as a highly effective counter-defence system. Prophage-mediated viral defence offers an efficient mechanism for bacterial success in host-virus dynamics, and counter-defence promotes phage co-evolution.
+contributors:
+    - Hugo Vaysset
+relevantAbstract:
+    - 10.1038/nmicrobiol.2016.251
 ---
 
-# MMB_gp29_gp30
+# MMB gp29-gp30
 
-## To do 
+## Description
+MMB gp29-gp30 is a defense system which was in the MichelleMyBell (MMB) temperate mycobacteriophage. It is an example of prophage-mediated defense :ref{doi=10.1038/nmicrobiol.2016.251}.
+
+## Molecular mechanisms
+To the extent of our knowledge, the precise mechanism of action of MMB gp29-gp30 is not known. The system was shown to protect against lytic infection by temperate phage (e.g. phage Tweety) and does not act through abotive infection. Cells that survive infection tend to become lysogens for the infecting phage. It was also shown that the expression of gp29 alone was toxic in *M. smegmatis* :ref{doi=10.1038/nmicrobiol.2016.251}.
 
 ## Example of genomic structure
 
@@ -77,11 +85,3 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstract
-::relevant-abstracts
----
-items:
-    - doi: 10.1038/nmicrobiol.2016.251
-
----
-::

content/3.defense-systems/mok_hok_sok.md

@@ -10,9 +10,26 @@ tableColumns:
     Activator: Unknown
     Effector: Unknown
     PFAM: PF01848
+relevantAbstracts:
+    - doi: 10.1128/jb.178.7.2044-2050.1996
+    - doi: 10.1016/0022-2836(92)90714-u 
+contributors:
+    - Jean Cury
 ---
 
 # Mok_Hok_Sok
+
+## Description
+
+The Mok Hok Sok system was discovered as a type 1 toxin-antitoxin system to stabilize plasmid R1 :ref{doi=10.1128/jb.161.1.292-298.1985}. Sok (Suppression of Killing) is an RNA and serves as the antitoxin. Hok (Host killing) is the toxin and Mok (Modulation of killing) is required for the expression of Hok :ref{doi=10.1016/j.mib.2007.03.003,10.1093/nar/gkl750}.
+Hok/sok are not related to the T4 head protein Hoc and Soc.
+This system defends against T4 phages only, as far as we currently know.
+
+## Molecular mechanism
+
+Upon infection of phage T4, the transcription is halted by the phage, which leads to a decreasing level of the antitoxin Sok within a few minutes. The Hok proteins manage to be process in their active form and trigger cell death by depolarization of the membrane :ref{doi=10.1006/jmbi.1995.0186} before the later stage of the phage infection (assembly, packaging and lysis).
+
+
 ## Example of genomic structure
 
 The Mok_Hok_Sok is composed of 2 proteins: Mok and Hok.
@@ -51,7 +68,7 @@ graph LR;
     Pecota_1996[<a href='https://doi.org/10.1128/jb.178.7.2044-2050.1996'>Pecota and  Wood, 1996</a>] --> Origin_0
     Origin_0[R1 plasmid of Salmonella paratyphi 
 <a href='https://ncbi.nlm.nih.gov/protein/WP_001372321.1'>WP_001372321.1</a>] --> Expressed_0[Escherichia coli]
-    Expressed_0[Escherichia coli] ----> T4 & LambdaVir
+    Expressed_0[Escherichia coli] ----> T4
     subgraph Title1[Reference]
         Pecota_1996
 end
@@ -63,20 +80,10 @@ end
 end
     subgraph Title4[Phage infected]
         T4
-        LambdaVir
 end
     style Title1 fill:none,stroke:none,stroke-width:none
     style Title2 fill:none,stroke:none,stroke-width:none
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
-    - doi: 10.1128/jb.178.7.2044-2050.1996
-
----
-::
 

content/3.defense-systems/shosta.md

@@ -10,9 +10,23 @@ tableColumns:
     Activator: Unknown
     Effector: Unknown
     PFAM: PF02481
+relevantAbstracts:
+  - doi: 10.1016/j.chom.2022.09.017
+  - doi: 10.1016/j.chom.2022.02.018
+  - doi: 10.1101/gr.133850.111
 ---
 
 # ShosTA
+
+## Description
+
+ShosTA system was first described as a Toxin/Antitoxin system in 2012 :ref{doi=10.1101/gr.133850.111} without demonstration of antiphage activity. In 2022, a paper described the same system as "DprA + PRTase" inside P2 like prophages and prooves its antiphage activity. Finally, the antiphage activity was also prooved in another study with the original name ShosTA :ref{doi=10.1016/j.chom.2022.09.017}.
+
+This system is composed of two protein: ShosT and ShosA encoding for Hydrolase/PRTase and DprA (nucleotid binding) respectively.
+
+## Molecular mechanism
+The ShosTA system is a toxin (ShosT) antitoxin (ShosA) system. The domains of ShosT (Hydrolase and PRTase) allows us to hypothesize a toxicity linked to host protein degradation.
+
 ## Example of genomic structure
 
 The ShosTA is composed of 2 proteins: ShosA and ShosT.
@@ -88,15 +102,5 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstracts
 
-::relevant-abstracts
----
-items:
-    - doi: 10.1016/j.chom.2022.09.017
-    - doi: 10.1016/j.chom.2022.09.017
-    - doi: 10.1101/gr.133850.111
-
----
-::
 

content/3.defense-systems/viperin.md

@@ -7,28 +7,32 @@ tableColumns:
       abstract: |
         Viperin is an interferon-induced cellular protein that is conserved in animals. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3'-deoxy-3',4'-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems.
     Sensor: Unknown
-    Activator: Direct
+    Activator: Direct binding
     Effector: Nucleotide modifying
     PFAM: PF04055, PF13353
+contributors:
+    - Marian Dominguez-Mirazo
+relevantAbstracts:
+    - doi: 10.1038/s41586-020-2762-2
 ---
 
 # Viperin
 ## Description
  
-Viperins, for "Virus Inhibitory Protein, Endoplasmic Reticulum-associated, INterferon-inducible", are antiviral enzymes whose expression is stimulated by interferons in eukaryotic cells. They are important components of eukaryotic innate immunity, and present antiviral activity against a wide diversity of viruses, including double-stranded DNA viruses, single-strand RNA viruses and retroviruses (1).  
+Viperins, for "Virus Inhibitory Protein, Endoplasmic Reticulum-associated, INterferon-inducible", are antiviral enzymes whose expression is stimulated by interferons in eukaryotic cells. They are important components of eukaryotic innate immunity, and present antiviral activity against a wide diversity of viruses, including double-stranded DNA viruses, single-strand RNA viruses and retroviruses :ref{doi=10.1146/annurev-virology-011720-095930}.  
 
-Recently,  Viperin-like enzymes were found in prokaryotes (pVips).  Strikingly, like their eukaryotic counter-part with eukaryotic viruses, pVips provide clear protection against phage infection to their host, and therefore constitute a new defense system (2). Like eukaryotic Viperins, pVips produce modified nucleotides that block phage transcription, acting as chain terminators. They constitute a form of chemical defense. A recent study reported that pVips can be found in around 0.5% of prokaryotic genomes (3).
+Recently,  Viperin-like enzymes were found in prokaryotes (pVips).  Strikingly, like their eukaryotic counter-part with eukaryotic viruses, pVips provide clear protection against phage infection to their host, and therefore constitute a new defense system :ref{doi=10.1038/s41586-020-2762-2}. Like eukaryotic Viperins, pVips produce modified nucleotides that block phage transcription, acting as chain terminators. They constitute a form of chemical defense. A recent study reported that pVips can be found in around 0.5% of prokaryotic genomes :ref{doi=10.1038/s41467-022-30269-9}.
 
 ## Molecular mechanism
 
+!Figure1](/viperin/human_vip.jpg){max-width=750px}
+Fig.1: Catalytic activity of human Viperin generates ddhCTP :ref{doi=10.1002/1873-3468.13778}
 
-Fig.1: Catalytic activity of human Viperin generates ddhCTP (Ebrahimi et al. al., 2020)
-
-Viperins are members of the radical S-adenosylmethionine (rSAM) superfamily. This group of enzymes use a [4Fe-4S] cluster to cleave S-adenosylmethionine (SAM) reductively, generating a radical which is generally transferred to a substrate. It was demonstrated that through their [4Fe-4S] cluster catalytic activity, eukaryotic viperins convert a ribonucleotide, the cytidine triphosphate (CTP) into a modified ribonucleotide, the 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) (4,5). 
+Viperins are members of the radical S-adenosylmethionine (rSAM) superfamily. This group of enzymes use a [4Fe-4S] cluster to cleave S-adenosylmethionine (SAM) reductively, generating a radical which is generally transferred to a substrate. It was demonstrated that through their [4Fe-4S] cluster catalytic activity, eukaryotic viperins convert a ribonucleotide, the cytidine triphosphate (CTP) into a modified ribonucleotide, the 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) :ref{doi=10.1038/s41586-018-0238-4}. 
 
-Prokaryotic Viperins also convert ribonucleotides triphosphate into modified ribonucleotides, but contrary to their eukaryotic counterparts can use a diversity of substrates to produce  ddhCTP,  or ddh-guanosine triphosphate (ddhGTP), or ddh-uridine triphosphate (ddhUTP), or several of these nucleotides for certain pVips (2).
+Prokaryotic Viperins also convert ribonucleotides triphosphate into modified ribonucleotides, but contrary to their eukaryotic counterparts can use a diversity of substrates to produce  ddhCTP, or ddh-guanosine triphosphate (ddhGTP), or ddh-uridine triphosphate (ddhUTP), or several of these nucleotides for certain pVips :ref{doi=10.1038/s41586-020-2762-2}.
 
-Compared to the initial ribonucleotide triphosphate, the modified ddh-nucleotide product of Viperins lacks a hydroxyl group at the 3′ carbon of the ribose (Fig.1). The ddh-nucleotides produced by Viperins can be used as substrates by some viral RNA polymerases. Because of their lost hydroxyl group at the 3’carbon of the ribose, once incorporated into the newly forming viral RNA chain, these ddh-nucleotides act as chain terminators. By preventing further polymerization of the viral RNA chain, ddh-nucleotides can inhibit viral replication (2,4,5).
+Compared to the initial ribonucleotide triphosphate, the modified ddh-nucleotide product of Viperins lacks a hydroxyl group at the 3′ carbon of the ribose (Fig.1). The ddh-nucleotides produced by Viperins can be used as substrates by some viral RNA polymerases. Because of their lost hydroxyl group at the 3’carbon of the ribose, once incorporated into the newly forming viral RNA chain, these ddh-nucleotides act as chain terminators. By preventing further polymerization of the viral RNA chain, ddh-nucleotides can inhibit viral replication :ref{doi=10.1038/s41586-020-2762-2,10.1038/s41586-018-0238-4}.
 
 ## Example of genomic structure
 
@@ -223,13 +227,4 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
-    - doi: 10.1038/s41586-020-2762-2
-
----
-::