content/1.help/_dir.yml

-navigation.icon: "md:help"
+navigation.icon: 'i-tabler:help'
 

content/2.general-concepts/1.abortive-infection.md

@@ -19,6 +19,7 @@ relevantAbstracts:
   - doi: 10.1038/s41579-023-00934-x
 ---
 
+# Abortive Infection
 
 The term abortive infection was coined in the 1950s :ref{doi=10.1128/jb.68.1.36-42.1954} 
 to describe the observations that a fraction of the bacterial population did not support phage replication. 

content/2.general-concepts/6.defensive-domains.md

@@ -5,8 +5,9 @@ toc: true
 contributors:
     - Hugo Vaysset
 ---
+# Defensive Domains
 
-# 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. 
 
@@ -14,10 +15,10 @@ Proteins can typically be decomposed into a set of structural or functional unit
 
 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}.
 
-# 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}. 
 
-# Domains can be conserved throughout evolution
+## Domains can be conserved throughout evolution
 
 It is clear that some defense systems can be conserved among different clades of bacteria but it was also observed that the unit of evolutionary conservation can be the protein domain :ref{doi=10.1038/s41467-022-30269-9}. As a consequence, it is frequent to find the same domain associated with a wide range of distinct other domains in different defense systems :ref{doi=10.1016/j.mib.2023.102312}. This is well illustrated by defense systems such [Avs](/defense-systems/avs) or [CBASS](/defense-systems/cbass) that can be constituted of diverse effector proteins which differ from each other based on the specific domains that compose them :ref{doi=10.1126/science.aba0372}, :ref{doi=10.1038/s41564-022-01239-0}, :ref{doi=10.1038/s41564-020-0777-y}. The modular aspect of protein domains fits with the concept of "evolution as tinkering" stating that already existing objects (here protein domains) can often be repurposed in new manners, allowing the efficient development of novel functions :ref{doi=10.1126/science.860134}.

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

@@ -4,5 +4,6 @@ contributors:
     - Marian Dominguez-Mirazo
 layout: article
 ---
+# Defense Systems and Mobile Genetic Elements
 
 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/2.general-concepts/_dir.yml

-navigation.icon: "md:history_edu"
+navigation.icon: 'i-mdi:book-education-outline'
 

content/3.defense-systems/_dir.yml

 title: Defense Systems
-navigation.icon: 'md:list'
\ No newline at end of file
+navigation.icon: 'i-tabler:virus-off'
\ No newline at end of file

content/3.defense-systems/aditi.md

@@ -10,11 +10,22 @@ tableColumns:
     Activator: Unknown
     Effector: Unknown
     PFAM: PF18928
+contributors:
+    - Rachel Lavenir
 relevantAbstracts:
     - doi: 10.1016/j.chom.2022.09.017
 ---
 
 # Aditi
+## Description
+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 named after the Hindu guardian goddess of all life.
+
+## Molecular mechanisms
+As far as we are aware, the molecular mechanism is unknown. 
+
 ## Example of genomic structure
 
 The Aditi is composed of 2 proteins: DitA and DitB.
@@ -47,7 +58,6 @@ height: 700
 dataUrls:
    - /aditi/Aditi.Aditi__DitB.0.V.cif
    - /aditi/Aditi.Aditi__DitA.0.V.cif
-
 ---
 ::
 
@@ -79,3 +89,4 @@ end
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
 
+

content/3.defense-systems/avs.md

@@ -11,26 +11,35 @@ tableColumns:
     Effector: Diverse effectors (Nucleic acid degrading, putative Nucleotide modifying, putative Membrane disrupting)
 
     PFAM: PF00753, PF13289, PF13365
+contributors: 
+    - Alex Linyi Gao
+    - Nathalie Bechon
 relevantAbstracts:
     - doi: 10.1126/science.aba0372
     - doi: 10.1126/science.abm4096
-contributors: 
-    - Alex Linyi Gao
 ---
 
 # Avs
 
 ## Description 
-Avs proteins are members of the STAND (signal transduction ATPase with numerous domains) superfamily of P-loop NTPases, which play essential roles in innate immunity and programmed cell death in eukaryotes (E. V. Koonin et al., Cell Death Differ. 9, 394–404 (2002). doi: 10.1038/sj.cdd.4400991; D. D. Leipe et al., J. Mol. Biol. 343, 1–28 (2004). doi: 10.1016/j.jmb.2004.08.023). STAND ATPases include nucleotide-binding oligomerization domain-like receptors (NLRs) in animal inflammasomes and plant resistosomes. They share a common tripartite domain architecture, typically consisting of a central ATPase, a C-terminal sensor with superstructure-forming repeats, and an N-terminal effector involved in inflammation or cell death.
+Avs proteins are members of the STAND (signal transduction ATPase with numerous domains) superfamily of P-loop NTPases, which play essential roles in innate immunity and programmed cell death in eukaryotes :ref{doi=10.1038/sj.cdd.4400991,10.1016/j.jmb.2004.08.023}. STAND ATPases include nucleotide-binding oligomerization domain-like receptors (NLRs) in animal inflammasomes and plant resistosomes. Bacterial Avs share a common tripartite domain architecture with eukaryotic NLR, typically consisting of a central ATPase, a C-terminal sensor with superstructure-forming repeats, and an N-terminal effector involved in inflammation or cell death. They are very similar to other bacterial defense systems: [bNACHT](/defense-systems/nlr), [CARD_NLR](/defense-systems/card_nlr) , [Rst_TIR-NLR](/defense-systems/rst_tir-nlr). 
 
 ## Molecular mechanism
+
+::info
+Two classifications of Avs systems were proposed. The first one :ref{doi=10.1126/science.aba0372} distinguishes 5 types of Avs based on their effector domain. This is the classification used in Defense Finder right now, and in the following wiki entry unless stated otherwise. Considering the modular aspect of the effector domain, a new classification based on the homology of the NTPase and C terminal sensor domain, and not on the effector domain, has been proposed more recently :ref{doi=10.1126/science.abm4096} and is the one used in this description of the mechanism. This second classification defines 4 different types, that do not represent the whole diversity of Avs proteins but only the 4 characterized types.
+::
+
 Similar to their eukaryotic counterparts, Avs proteins utilize their C-terminal sensor domains to bind to pathogen-associated molecular patterns (PAMPs). Specifically, Avs1, Avs2, and Avs3 bind to monomers of the large terminase subunit of tailed phages, which account for approximately 96% of all phages, whereas Avs4 binds to monomers of the portal protein. The helical sensor domains of Avs1-4 can recognize diverse variants of terminase or portal proteins, with less than 5% sequence identity in some cases. Binding is mediated by shape complementarity across an extended interface, indicating fold recognition. Additionally, Avs3 directly recognizes active site residues and the ATP ligand of the large terminase.
 
 Upon binding to their cognate phage protein, Avs1-4 assemble into tetramers that activate their N-terminal effector domains, which are often non-specific dsDNA endonucleases. The effector domains are thought to induce abortive infection to disrupt the production of progeny phage.
 
+Avs systems sometimes include additional essential small genes on top of the canonical Avs gene, but the way they contribute to defense is not currently described.
+
+
 ## Example of genomic structure
 
-A total of 5 subsystems have been described for the Avs system.
+The Avs system have been describe in a total of 5 subsystems (in the old classification).
 
 Here is some examples found in the RefSeq database:
 
@@ -64,8 +73,6 @@ The system was detected in 366 different species.
 
 Proportion of genome encoding the Avs system for the 14 phyla with more than 50 genomes in the RefSeq database.
 
-
-
 ## Structure
 ### AVAST_I
 ##### Example 1

content/3.defense-systems/caprel.md

@@ -10,18 +10,21 @@ tableColumns:
     Activator: Direct
     Effector: Nucleic acid degrading (pyrophosphorylates tRNAs)
     PFAM: PF04607
+contributors: 
+  - Héloïse Georjon
+  - Florian Tesson
 relevantAbstracts:
-    - doi: 10.1038/s41586-022-05444-z
+  - doi: 10.1038/s41586-022-05444-z
 ---
 
 # CapRel
 ## Description
 
-CapRel is a fused toxin–antitoxin system that is active against diverse phages when expressed in *Escherichia coli*. CapRel belongs to the family of toxSAS toxin–antitoxin systems. CapRel is an Abortive infection system which is found in Cyanobacteria, Actinobacteria, and Proteobacteria, Spirochetes, Bacteroidetes, and Firmicutes, as well as in some temperate phages.
+CapRel is a fused toxin-antitoxin system that is active against diverse phages when expressed in *Escherichia coli* :ref{doi=10.1038/s41586-022-05444-z}. CapRel belongs to the family of toxSAS toxin-antitoxin systems. CapRel is an Abortive infection system which is found in Cyanobacteria, Actinobacteria, and Proteobacteria, Spirochetes, Bacteroidetes, and Firmicutes, as well as in some temperate phages.
 
 ## Molecular mechanism
 
-The CapRel system of Salmonella temperate phage SJ46 is normally found in a closed conformation, which is thought to maintain CapRel in an auto-inhibited state. However during phage SECPhi27 infection, binding of the major phage capsid protein (Gp57) to CapRel releases it from is inhibited state, allowing pyrophosphorylation of tRNAs by the toxin domain and resulting in translation inhibition. Other phage capsid proteins can be recognized by CapRel, as observed during infection by phage Bas8.
+The CapRel system of Salmonella temperate phage SJ46 is normally found in a closed conformation, which is thought to maintain CapRel in an auto-inhibited state. However during phage SECPhi27 infection, binding of the major phage capsid protein (Gp57) to CapRel releases it from is inhibited state, allowing pyrophosphorylation of tRNAs by the toxin domain and resulting in translation inhibition :ref{doi=10.1038/s41586-022-05444-z}. Other phage capsid proteins can be recognized by CapRel, as observed during infection by phage Bas8.
 
 
 Different CapRel homologues confer defense against different phages, suggesting variable phage specificity of CapRel system which seems to be mediated by the C-terminal region of CapRel. 
@@ -105,4 +108,3 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-

content/3.defense-systems/detocs.md

@@ -138,11 +138,6 @@ end
     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
-<<<<<<< content/3.defense-systems/detocs.md
 </mermaid>
 
 
-=======
-</mermaid>
->>>>>>> content/3.defense-systems/detocs.md
-

content/3.defense-systems/dodola.md

@@ -20,11 +20,12 @@ relevantAbstracts:
 
 ## Description
 
-Dodola is named after a figure from Slavic mythology, often associated with rain and fertility. The Dodola defense system was first discovered through its common association with known defense systems, and characterized in B. subtilis, demonstrating its efficacy against the SPP1 phage. It is composed of two proteins, DolA and DolB
+Dodola is named after a figure from Slavic mythology, often associated with rain and fertility. The Dodola defense system was first discovered through its common association with known defense systems, and characterized in B. subtilis, demonstrating its efficacy against the SPP1 phage :ref{doi=10.1016/j.chom.2022.09.017}.
+Dodola is composed of two proteins, DolA and DolB. DolA contains a DUF6414 domain, and DolB contains a ClpB-like domain.
 
 ## Molecular mechanisms
 
-The molecular mechanism is unknown. DolA contains a DUF6414 domain, and DolB contains a ClpB-like domain.
+As far as we are aware, the molecular mechanism is unknown.
 
 ## Example of genomic structure
 

content/3.defense-systems/druantia.md

@@ -10,11 +10,22 @@ tableColumns:
     Activator: Unknown
     Effector: Unknown
     PFAM: PF00145, PF00270, PF00271, PF04851, PF09369, PF14236
+contributors: 
+  - Lucas Paoli
 relevantAbstracts:
-    - doi: 10.1126/science.aar4120
+  - doi: 10.1126/science.aar4120
 ---
 
 # Druantia
+
+## Description
+
+The Druantia system was described by Doron et al. 2018 :ref{doi=10.1126/science.aar4120} and includes multiple subtypes, including type I (DruABCDE), type II (DruMFGE), and Type III (DruHE). Druantia is a particularly large system (~12 kb) and was named after the Gallic tree goddess. Type III was further tested by Wang et al. 2023 :ref{doi=10.1128/jvi.00599-23}.
+
+## Molecular mechanisms
+
+As far as we are aware, the molecular mechanism is unknown. 
+
 ## Example of genomic structure
 
 A total of 3 subsystems have been described for the Druantia system.

content/3.defense-systems/eleos.md

@@ -10,16 +10,26 @@ tableColumns:
     Activator: Unknown
     Effector: Unknown
     PFAM: PF00350, PF01926, PF18709
+contributors: 
+    - Alba Herrero del Valle
 relevantAbstracts:
     - doi: 10.1016/j.chom.2022.09.017
+    - doi: 10.1101/2022.12.12.520048
 ---
 
 # Eleos
-The Eleos system was previously described as the Dynamins-like system in (Millman et al, 2022).
+
+## Description
+
+\The Eleos (for the greek goddess of mercy) system was previously described as the Dynamins-like system in :ref{doi=10.1016/j.chom.2022.09.017}. It is formed by the LeoA and LeoBC proteins. LeoBC has been found to be analogous to GIMAPs (GTPases immunity-associated proteins), that are interferon inducible :ref{doi=10.1101/2022.12.12.520048}. LeoA in *E. coli* ETEC H10407 localises to the periplasm and has been suggested to potientiate bacterial virulence. Its crystal structure has been solved :ref{doi=10.1371/journal.pone.0107211}. Eleos from *Bacillus vietnamensis* NBRC 101237 has been found to protect against jumbo-phages in *Bacillus subtilis* :ref{doi=10.1016/j.chom.2022.09.017}.
+
+## Molecular mechanism
+
+As far as we are aware, the molecular mechanism is unknown. 
 
 ## Example of genomic structure
 
-The Eleos is composed of 4 proteins: LeoA, LeoBC, LeoB and LeoC.
+The Eleos system is composed of 2 proteins: LeoA and, LeoBC. Sometimes, the system is in three genes: LeoA, LeoB and LeoC.
 
 Here is an example found in the RefSeq database:
 
@@ -40,6 +50,18 @@ Proportion of genome encoding the Eleos system for the 14 phyla with more than 5
 
 
 ## Structure
+### Experimentaly determined structure
+From :ref{doi=10.1371/journal.pone.0107211} in *Escherichia coli* (ETEC) strain H10407:
+
+::molstar-pdbe-plugin
+---
+height: 700
+dataUrl: /eleos/4aur_LeoA_1mer.pdb
+---
+::
+
+
+
 ### Eleos
 ##### Example 1
 
@@ -79,4 +101,3 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
-

content/3.defense-systems/fs_sma.md

@@ -7,27 +7,34 @@ tableColumns:
       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.
     PFAM: PF02452
+contributors:
+    - Héloïse Georjon
 relevantAbstracts:
-    - doi: 10.1016/j.cell.2022.07.014
+  - doi: 10.1016/j.cell.2022.07.014
 ---
 
 # FS_Sma
 
-## To do 
+## Description
+SMA (single-protein MazF-like antiphage system) was identified in a phage-inducible chromosomal island (PICI) found in *Staphylococcus aureus* :ref{doi=10.1016/j.cell.2022.07.014}. SMA was shown to inhibit phage infection and to inhibit the formation of new virions after prophage induction.
+
+## Molecular mechanisms
+The SMA protein comprises a domain analogous to MazF. MazF a protein that is normally part of the MazEF toxin-antitoxin systems, in which MazF is a toxic endoribonuclease that targets mRNA :ref{doi=10.1016/s1097-2765(03)00402-7}.
+As far as we are aware, the precise molecular mechanism of SMA is unknown.
 
 ## Example of genomic structure
 
-The FS_Sma is composed of 1 protein: Sma.
+The Sma is composed of 1 protein: Sma.
 
 Here is an example found in the RefSeq database:
 
 ![fs_sma](/fs_sma/FS_Sma.svg){max-width=750px}
 
-The FS_Sma system in *Staphylococcus aureus* (GCF_022869625.1, NZ_CP064365) is composed of 1 protein: Sma (WP_000041883.1) 
+The Sma system in *Staphylococcus aureus* (GCF_022869625.1, NZ_CP064365) is composed of 1 protein: Sma (WP_000041883.1) 
 
 ## Distribution of the system among prokaryotes
 
-Among the 22,803 complete genomes of RefSeq, the FS_Sma is detected in 578 genomes (2.53 %).
+Among the 22,803 complete genomes of RefSeq, the Sma is detected in 578 genomes (2.53 %).
 
 The system was detected in 20 different species.
 

content/3.defense-systems/gabija.md

@@ -56,6 +56,19 @@ Proportion of genome encoding the Gabija system for the 14 phyla with more than
 
 
 ## Structure
+
+### Experimentaly determined structure
+From :ref{doi=10.1038/s41586-023-06855-2} in *Bacillus cereus* VD045:
+
+::molstar-pdbe-plugin
+---
+height: 700
+dataUrls: 
+    - /gabija/8sm3-assembly1_BcGajAB_4_4mer.cif
+    - /gabija/8u7i-assembly1_BcGajAB_4_4mer_gad1.cif
+---
+::
+
 ### Gabija
 ##### Example 1
 

content/3.defense-systems/gaps4.md

@@ -6,13 +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.
+contributors:
+    - Hugo Vaysset
 relevantAbstracts:
     - doi: 10.1101/2023.03.28.534373
 ---
 
 # GAPS4
 
-## To do 
+## Description
+GAPS4 is a two genes system (GAPS4a and GAPS4b). GAPS stands for GMT-encoded Anti-Phage System. 
+
+GAPS4 is present in both Gram positive and Gram negative 
+GAPS4 activity was assessed in *E. coli* and was shown to be active against T4, P1-vir and lambda-vir and to reduce lysis plaque size of T7 :ref{doi=10.1101/2023.03.28.534373}. 
+
+## Molecular mechanism
+GAPS4a is a nuclease containing a domain from the PDDEXK clan (CL0236) suggesting that the GAPS4 defense system is acting via DNA degradation. Both genes are required for phage defense and were predicted to form a heterodimer. It was shown that the system works causes host DNA degradation upon infection by lambda-vir only, which would suggest that GAPS4 is an abortive infection system :ref{doi=10.1101/2023.03.28.534373}.
+
 
 ## Example of genomic structure
 
@@ -37,6 +47,7 @@ Proportion of genome encoding the GAPS4 system for the 14 phyla with more than 5
 
 
 ## Structure
+
 ### GAPS4
 ##### Example 1
 

content/3.defense-systems/gaps6.md

@@ -6,14 +6,37 @@ 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.
-relevantAbstracts:
+contributors:
+    - Jean Cury
+relevantAbstract:
     - doi: 10.1101/2023.03.28.534373
 ---
 
 # GAPS6
 
-## To do 
+## Description
 
+<<<<<<< content/3.defense-systems/gaps6.md
+GAPS (GMT-encoded Anti-Phage System) antiphage systems were discovered on newly described Gamma-Mobile-Trio elements. 
+
+GAPS6 is composed of two proteins, [GAPS6a](https://www.ncbi.nlm.nih.gov/protein/WP_248387294.1/) and [GAPS6b](https://www.ncbi.nlm.nih.gov/protein/WP_248387295.1/). These two proteins are encoded together in diverse Gram-negative bacteria.
+
+## Molecular mechanism
+
+GAPS6b is essential for the defense phenotype, however it is not known whether GAPS6b could be sufficient.
+GAPS6b is composed of TPR repeats at the N-terminus, possibly allowing ligand binding and a predicted RNAse domain (PINc, PF08745.14) at the C-terminus. PINc domains have been implicated as toxins in bacterial toxin-antitoxin modules :ref{doi=10.1093/protein/gzq081}. The PINc domain is required for the anti-phage defense activity of GAPS6.
+
+## Example of genomic structure
+
+TODO
+
+## Distribution
+
+TODO
+
+## Predicted structure
+
+=======
 ## Example of genomic structure
 
 The GAPS6 is composed of 2 proteins: GAPS6a and GAPS6b.
@@ -37,6 +60,7 @@ Proportion of genome encoding the GAPS6 system for the 14 phyla with more than 5
 
 
 ## Structure
+>>>>>>> content/3.defense-systems/gaps6.md
 ### GAPS6
 ##### Example 1
 
@@ -68,9 +92,7 @@ end
         Expressed_0
 end
     subgraph Title4[Phage infected]
-        T7
         T4
-        P1-vir
         Lambda-vir
 end
     style Title1 fill:none,stroke:none,stroke-width:none
@@ -78,4 +100,7 @@ end
     style Title3 fill:none,stroke:none,stroke-width:none
     style Title4 fill:none,stroke:none,stroke-width:none
 </mermaid>
+<<<<<<< content/3.defense-systems/gaps6.md
+=======
 
+>>>>>>> content/3.defense-systems/gaps6.md

content/3.defense-systems/isg15-like.md

@@ -3,18 +3,30 @@ title: ISG15-like
 layout: article
 tableColumns:
     article:
-      doi: 10.1016/j.chom.2022.09.017
+      doi: 10.1101/2023.09.04.556158
       abstract: |
-        Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection.
+        Multiple immune pathways in humans conjugate ubiquitin-like proteins to virus and host molecules as a means of antiviral defense. Here we studied an anti-phage defense system in bacteria, comprising a ubiquitin-like protein, ubiquitin-conjugating enzymes E1 and E2, and a deubiquitinase. We show that during phage infection, this system specifically conjugates the ubiquitin-like protein to the phage central tail fiber, a protein at the tip of the tail that is essential for tail assembly as well as for recognition of the target host receptor. Following infection, cells encoding this defense system release a mixture of partially assembled, tailless phage particles, and fully assembled phages in which the central tail fiber is obstructed by the covalently attached ubiquitin-like protein. These phages exhibit severely impaired infectivity, explaining how the defense system protects the bacterial population from the spread of phage infection. Our findings demonstrate that conjugation of ubiquitin-like proteins is an antiviral strategy conserved across the tree of life.
     Sensor: Unknown
     Activator: Unknown
-    Effector: Unknown
+    Effector: Protein modifying
+contributors: 
+  - Alba Herrero del Valle
 relevantAbstracts:
-    - doi: 10.1016/j.chom.2022.09.017
-
+  - doi: 10.1016/j.chom.2022.09.017
+  - doi: 10.1101/2023.09.04.556158
 ---
 
+
 # ISG15-like
+
+## Description
+
+ISG15-like (Interferon-stimulated gene 15 - like) systems (also known as Bil systems for Bacterial ISG15-like systems) are a 4 gene defense system comprising a homolog of ubiquitin-like ISG15 (BilA), ubiquitin-conjugating enzymes E1 (BilD) and E2 (BilB), and a deubiquitinase (BilC) :ref{doi=10.1101/2023.09.04.556158,10.1016/j.chom.2022.09.017}. It has been shown to defend against muliple coliphages :ref{doi=10.1016/j.chom.2022.09.017}. The Bil system is analogous to the ISG15 system in humans, that protects against virus.
+
+## Molecular mechanism
+
+Hör et al., have shown that the ISG15-like system defends bacteria against phages by impairing infectivity of newly synthezised phages. It does so by preventing tail assembly that leads to non-infective tailless phages or by producing modified tails with an obstructed tail tip that are not capable of infecting. More specifically, BilA is conjugated to the central tail fiber (CTF) protein of the phage :ref{doi=10.1101/2023.09.04.556158}.
+
 ## Example of genomic structure
 
 The ISG15-like is composed of 4 proteins: BilA, BilB, BilC and BilD.
@@ -50,58 +62,6 @@ dataUrls:
    - /isg15-like/ISG15-like.ISG15-like__BilB.4.V.cif
    - /isg15-like/ISG15-like.ISG15-like__BilA.2.V.cif
 
----
-::
-##### Example 2
-
-::molstar-pdbe-plugin
----
-height: 700
-dataUrls:
-   - /isg15-like/ISG15-like.ISG15-like__BilD.3.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilC.2.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilB.4.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilA.2.V.cif
-
----
-::
-##### Example 3
-
-::molstar-pdbe-plugin
----
-height: 700
-dataUrls:
-   - /isg15-like/ISG15-like.ISG15-like__BilA.2.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilB.4.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilC.2.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilD.3.V.cif
-
----
-::
-##### Example 4
-
-::molstar-pdbe-plugin
----
-height: 700
-dataUrls:
-   - /isg15-like/ISG15-like.ISG15-like__BilA.2.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilB.4.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilC.2.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilD.3.V.cif
-
----
-::
-##### Example 5
-
-::molstar-pdbe-plugin
----
-height: 700
-dataUrls:
-   - /isg15-like/ISG15-like.ISG15-like__BilA.2.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilB.4.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilC.2.V.cif
-   - /isg15-like/ISG15-like.ISG15-like__BilD.3.V.cif
-
 ---
 ::
 

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

@@ -30,7 +30,7 @@ Lamassu has been suggested to be a large family of defense systems, that can be
 
 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}.
+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}. The DdmABC system corresponds to a Lamassu-Fam Cap4 nuclease system.
 
 ## Molecular mechanism
 

content/3.defense-systems/nixi.md

@@ -10,7 +10,7 @@ tableColumns:
     Activator: Unknown
     Effector: Nucleic acid degrading
 contributors:
-    - Marian Dominguez Mirazo 
+    - Marian Dominguez-Mirazo 
 relevantAbstracts:
     - doi: 10.1093/nar/gkac002
 ---