From 4df63827688b0d44b8e420cc2f482fe5a4a7d486 Mon Sep 17 00:00:00 2001
From: jeanrjc <jean.cury@normalesup.org>
Date: Wed, 27 Sep 2023 15:43:33 +0200
Subject: [PATCH] fix encoding and formatting issues

---
 content/2.defense-systems/caprel.md        | 6 +++---
 content/2.defense-systems/cbass.md         | 2 +-
 content/2.defense-systems/dctpdeaminase.md | 2 +-
 content/2.defense-systems/disarm.md        | 2 +-
 content/2.defense-systems/dmdde.md         | 2 +-
 content/2.defense-systems/dpd.md           | 2 +-
 content/2.defense-systems/gp29_gp30.md     | 2 +-
 content/2.defense-systems/lamassu-fam.md   | 4 ++--
 content/2.defense-systems/mqsrac.md        | 2 +-
 content/2.defense-systems/nixi.md          | 2 +-
 content/2.defense-systems/pago.md          | 3 +--
 content/2.defense-systems/pycsar.md        | 3 +--
 content/2.defense-systems/radar.md         | 2 +-
 content/2.defense-systems/rnlab.md         | 2 +-
 content/2.defense-systems/sefir.md         | 2 +-
 content/2.defense-systems/shango.md        | 2 +-
 content/2.defense-systems/spbk.md          | 2 +-
 content/2.defense-systems/viperin.md       | 6 +++---
 18 files changed, 23 insertions(+), 25 deletions(-)

diff --git a/content/2.defense-systems/caprel.md b/content/2.defense-systems/caprel.md
index 511124ba..ee88be4f 100644
--- a/content/2.defense-systems/caprel.md
+++ b/content/2.defense-systems/caprel.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1038/s41586-022-05444-z
       abstract: |
-        Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages1–3. Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns4 (PAMPs), many bacterial immune systems that respond to bacteriophage infection require phage-specific triggers to be activated. However, the identities of such triggers and the sensing mechanisms remain largely unknown. Here we identify and investigate the anti-phage function of CapRelSJ46, a fused toxin–antitoxin system that protects Escherichia coli against diverse phages. Using genetic, biochemical and structural analyses, we demonstrate that the C-terminal domain of CapRelSJ46 regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor. Following infection by certain phages, newly synthesized major capsid protein binds directly to the C-terminal domain of CapRelSJ46 to relieve autoinhibition, enabling the toxin domain to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for toxin–antitoxin-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a ‘Red Queen conflict’5, revealing a new front in the intense coevolutionary battle between phages and bacteria. Given that capsid proteins of some eukaryotic viruses are known to stimulate innate immune signalling in mammalian hosts6–10, our results reveal a deeply conserved facet of immunity.
+        Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages. Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns4 (PAMPs), many bacterial immune systems that respond to bacteriophage infection require phage-specific triggers to be activated. However, the identities of such triggers and the sensing mechanisms remain largely unknown. Here we identify and investigate the anti-phage function of CapRelSJ46, a fused toxini-antitoxin system that protects Escherichia coli against diverse phages. Using genetic, biochemical and structural analyses, we demonstrate that the C-terminal domain of CapRelSJ46 regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor. Following infection by certain phages, newly synthesized major capsid protein binds directly to the C-terminal domain of CapRelSJ46 to relieve autoinhibition, enabling the toxin domain to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for toxin-antitoxin-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a "Red Queen conflict", revealing a new front in the intense coevolutionary battle between phages and bacteria. Given that capsid proteins of some eukaryotic viruses are known to stimulate innate immune signalling in mammalian hosts, our results reveal a deeply conserved facet of immunity.
     Sensor: Sensing of phage protein
     Activator: Direct
     Effector: Nucleic acid degrading (pyrophosphorylates tRNAs)
@@ -14,7 +14,7 @@ tableColumns:
 # 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*. 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
 
@@ -66,4 +66,4 @@ items:
 
 
 ## References
-Zhang T, Tamman H, Coppieters 't Wallant K, Kurata T, LeRoux M, Srikant S, Brodiazhenko T, Cepauskas A, Talavera A, Martens C, Atkinson GC, Hauryliuk V, Garcia-Pino A, Laub MT. Direct activation of a bacterial innate immune system by a viral capsid protein. Nature. 2022 Dec;612(7938):132-140. doi: 10.1038/s41586-022-05444-z. Epub 2022 Nov 16. PMID: 36385533.
\ No newline at end of file
+Zhang T, Tamman H, Coppieters 't Wallant K, Kurata T, LeRoux M, Srikant S, Brodiazhenko T, Cepauskas A, Talavera A, Martens C, Atkinson GC, Hauryliuk V, Garcia-Pino A, Laub MT. Direct activation of a bacterial innate immune system by a viral capsid protein. Nature. 2022 Dec;612(7938):132-140. doi: 10.1038/s41586-022-05444-z. Epub 2022 Nov 16. PMID: 36385533.
diff --git a/content/2.defense-systems/cbass.md b/content/2.defense-systems/cbass.md
index 3f19ee4e..12d4998c 100644
--- a/content/2.defense-systems/cbass.md
+++ b/content/2.defense-systems/cbass.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1038/s41564-020-0777-y
       abstract: |
-        Cyclic-oligonucleotide-based anti-phage signalling systems (CBASS) are a family of defence systems against bacteriophages (hereafter phages) that share ancestry with the cGAS–STING innate immune pathway in animals. CBASS systems are composed of an oligonucleotide cyclase, which generates signalling cyclic oligonucleotides in response to phage infection, and an effector that is activated by the cyclic oligonucleotides and promotes cell death. Cell death occurs before phage replication is completed, therefore preventing the spread of phages to nearby cells. Here, we analysed 38,000 bacterial and archaeal genomes and identified more than 5,000 CBASS systems, which have diverse architectures with multiple signalling molecules, effectors and ancillary genes. We propose a classification system for CBASS that groups systems according to their operon organization, signalling molecules and effector function. Four major CBASS types were identified, sharing at least six effector subtypes that promote cell death by membrane impairment, DNA degradation or other means. We observed evidence of extensive gain and loss of CBASS systems, as well as shuffling of effector genes between systems. We expect that our classification and nomenclature scheme will guide future research in the developing CBASS field.
+        Cyclic-oligonucleotide-based anti-phage signalling systems (CBASS) are a family of defence systems against bacteriophages (hereafter phages) that share ancestry with the cGAS-STING innate immune pathway in animals. CBASS systems are composed of an oligonucleotide cyclase, which generates signalling cyclic oligonucleotides in response to phage infection, and an effector that is activated by the cyclic oligonucleotides and promotes cell death. Cell death occurs before phage replication is completed, therefore preventing the spread of phages to nearby cells. Here, we analysed 38,000 bacterial and archaeal genomes and identified more than 5,000 CBASS systems, which have diverse architectures with multiple signalling molecules, effectors and ancillary genes. We propose a classification system for CBASS that groups systems according to their operon organization, signalling molecules and effector function. Four major CBASS types were identified, sharing at least six effector subtypes that promote cell death by membrane impairment, DNA degradation or other means. We observed evidence of extensive gain and loss of CBASS systems, as well as shuffling of effector genes between systems. We expect that our classification and nomenclature scheme will guide future research in the developing CBASS field.
     Sensor: Unknown
     Activator: Signaling molecules
     Effector: Divers (Nucleic acid degrading, Nucleotide modifying, Membrane disrupting)
diff --git a/content/2.defense-systems/dctpdeaminase.md b/content/2.defense-systems/dctpdeaminase.md
index c5a18871..f4747904 100644
--- a/content/2.defense-systems/dctpdeaminase.md
+++ b/content/2.defense-systems/dctpdeaminase.md
@@ -20,7 +20,7 @@ Those systems can be found in plasmids (around 8%).
 ## Mechanism
 When activated by a phage infection, dCTPdeaminase, will convert deoxycytidine (dCTP/dCDP/dCMP) into deoxyuridine.
 This action will deplete the pool of CTP nucleotide necessary for the phage replication and will stop the infection.
-The trigger for dCTPdeaminase may be linked to the shutoff of RNAP (σS-dependent host RNA polymerase) that occur during phage infections.
+The trigger for dCTPdeaminase may be linked to the shutoff of RNAP (σS-dependent host RNA polymerase) that occur during phage infections.
 
 ## Example of genomic structure
 
diff --git a/content/2.defense-systems/disarm.md b/content/2.defense-systems/disarm.md
index b56b2cf3..6f040479 100644
--- a/content/2.defense-systems/disarm.md
+++ b/content/2.defense-systems/disarm.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1038/s41564-017-0051-0
       abstract: |
-        The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction–modification and CRISPR–Cas systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction–modification), which is widespread in bacteria and archaea. DISARM is composed of five genes, including a DNA methylase and four other genes annotated as a helicase domain, a phospholipase D (PLD) domain, a DUF1998 domain and a gene of unknown function. Engineering the Bacillus paralicheniformis 9945a DISARM system into Bacillus subtilis has rendered the engineered bacteria protected against phages from all three major families of tailed double-stranded DNA phages. Using a series of gene deletions, we show that four of the five genes are essential for DISARM-mediated defence, with the fifth (PLD) being redundant for defence against some of the phages. We further show that DISARM restricts incoming phage DNA and that the B. paralicheniformis DISARM methylase modifies host CCWGG motifs as a marker of self DNA akin to restriction–modification systems. Our results suggest that DISARM is a new type of multi-gene restriction–modification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses.
+        The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction–modification and CRISPR–Cas systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction–modification), which is widespread in bacteria and archaea. DISARM is composed of five genes, including a DNA methylase and four other genes annotated as a helicase domain, a phospholipase D (PLD) domain, a DUF1998 domain and a gene of unknown function. Engineering the Bacillus paralicheniformis 9945a DISARM system into Bacillus subtilis has rendered the engineered bacteria protected against phages from all three major families of tailed double-stranded DNA phages. Using a series of gene deletions, we show that four of the five genes are essential for DISARM-mediated defence, with the fifth (PLD) being redundant for defence against some of the phages. We further show that DISARM restricts incoming phage DNA and that the B. paralicheniformis DISARM methylase modifies host CCWGG motifs as a marker of self DNA akin to restriction–modification systems. Our results suggest that DISARM is a new type of multi-gene restriction–modification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses.
     Sensor: Unknown
     Activator: Unknown
     Effector: Unknown
diff --git a/content/2.defense-systems/dmdde.md b/content/2.defense-systems/dmdde.md
index 3633eb16..b77c8a64 100644
--- a/content/2.defense-systems/dmdde.md
+++ b/content/2.defense-systems/dmdde.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1038/s41586-022-04546-y
       abstract: |
-        Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements—in particular bacteriophages and plasmids—the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array of defences against these elements1. Here we identify two plasmid defence systems conserved in the Vibrio cholerae El Tor strains responsible for the ongoing seventh cholera pandemic2–4. These systems, termed DdmABC and DdmDE, are encoded on two major pathogenicity islands that are a hallmark of current pandemic strains. We show that the modules cooperate to rapidly eliminate small multicopy plasmids by degradation. Moreover, the DdmABC system is widespread and can defend against bacteriophage infection by triggering cell suicide (abortive infection, or Abi). Notably, we go on to show that, through an Abi-like mechanism, DdmABC increases the burden of large low-copy-number conjugative plasmids, including a broad-host IncC multidrug resistance plasmid, which creates a fitness disadvantage that counterselects against plasmid-carrying cells. Our results answer the long-standing question of why plasmids, although abundant in environmental strains, are rare in pandemic strains; have implications for understanding the dissemination of antibiotic resistance plasmids; and provide insights into how the interplay between two defence systems has shaped the evolution of the most successful lineage of pandemic V. cholerae.
+        Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements—in particular bacteriophages and plasmids—the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array of defences against these elements1. Here we identify two plasmid defence systems conserved in the Vibrio cholerae El Tor strains responsible for the ongoing seventh cholera pandemic2–4. These systems, termed DdmABC and DdmDE, are encoded on two major pathogenicity islands that are a hallmark of current pandemic strains. We show that the modules cooperate to rapidly eliminate small multicopy plasmids by degradation. Moreover, the DdmABC system is widespread and can defend against bacteriophage infection by triggering cell suicide (abortive infection, or Abi). Notably, we go on to show that, through an Abi-like mechanism, DdmABC increases the burden of large low-copy-number conjugative plasmids, including a broad-host IncC multidrug resistance plasmid, which creates a fitness disadvantage that counterselects against plasmid-carrying cells. Our results answer the long-standing question of why plasmids, although abundant in environmental strains, are rare in pandemic strains; have implications for understanding the dissemination of antibiotic resistance plasmids; and provide insights into how the interplay between two defence systems has shaped the evolution of the most successful lineage of pandemic V. cholerae.
 ---
 
 # DmdDE
diff --git a/content/2.defense-systems/dpd.md b/content/2.defense-systems/dpd.md
index 924a7005..76d72202 100644
--- a/content/2.defense-systems/dpd.md
+++ b/content/2.defense-systems/dpd.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1073/pnas.1518570113
       abstract: |
-        The discovery of ?20-kb gene clusters containing a family of paralogs of tRNA guanosine transglycosylase genes, called tgtA5, alongside 7-cyano-7-deazaguanine (preQ0) synthesis and DNA metabolism genes, led to the hypothesis that 7-deazaguanine derivatives are inserted in DNA. This was established by detecting 2’-deoxy-preQ0 and 2’-deoxy-7-amido-7-deazaguanosine in enzymatic hydrolysates of DNA extracted from the pathogenic, Gram-negative bacteria Salmonella enterica serovar Montevideo. These modifications were absent in the closely related S. enterica serovar Typhimurium LT2 and from a mutant of S. Montevideo, each lacking the gene cluster. This led us to rename the genes of the S. Montevideo cluster as dpdA-K for 7-deazapurine in DNA. Similar gene clusters were analyzed in ?150 phylogenetically diverse bacteria, and the modifications were detected in DNA from other organisms containing these clusters, including Kineococcus radiotolerans, Comamonas testosteroni, and Sphingopyxis alaskensis. Comparative genomic analysis shows that, in Enterobacteriaceae, the cluster is a genomic island integrated at the leuX locus, and the phylogenetic analysis of the TgtA5 family is consistent with widespread horizontal gene transfer. Comparison of transformation efficiencies of modified or unmodified plasmids into isogenic S. Montevideo strains containing or lacking the cluster strongly suggests a restriction–modification role for the cluster in Enterobacteriaceae. Another preQ0 derivative, 2’-deoxy-7-formamidino-7-deazaguanosine, was found in the Escherichia coli bacteriophage 9g, as predicted from the presence of homologs of genes involved in the synthesis of the archaeosine tRNA modification. These results illustrate a deep and unexpected evolutionary connection between DNA and tRNA metabolism.
+        The discovery of ?20-kb gene clusters containing a family of paralogs of tRNA guanosine transglycosylase genes, called tgtA5, alongside 7-cyano-7-deazaguanine (preQ0) synthesis and DNA metabolism genes, led to the hypothesis that 7-deazaguanine derivatives are inserted in DNA. This was established by detecting 2’-deoxy-preQ0 and 2’-deoxy-7-amido-7-deazaguanosine in enzymatic hydrolysates of DNA extracted from the pathogenic, Gram-negative bacteria Salmonella enterica serovar Montevideo. These modifications were absent in the closely related S. enterica serovar Typhimurium LT2 and from a mutant of S. Montevideo, each lacking the gene cluster. This led us to rename the genes of the S. Montevideo cluster as dpdA-K for 7-deazapurine in DNA. Similar gene clusters were analyzed in ?150 phylogenetically diverse bacteria, and the modifications were detected in DNA from other organisms containing these clusters, including Kineococcus radiotolerans, Comamonas testosteroni, and Sphingopyxis alaskensis. Comparative genomic analysis shows that, in Enterobacteriaceae, the cluster is a genomic island integrated at the leuX locus, and the phylogenetic analysis of the TgtA5 family is consistent with widespread horizontal gene transfer. Comparison of transformation efficiencies of modified or unmodified plasmids into isogenic S. Montevideo strains containing or lacking the cluster strongly suggests a restriction–modification role for the cluster in Enterobacteriaceae. Another preQ0 derivative, 2’-deoxy-7-formamidino-7-deazaguanosine, was found in the Escherichia coli bacteriophage 9g, as predicted from the presence of homologs of genes involved in the synthesis of the archaeosine tRNA modification. These results illustrate a deep and unexpected evolutionary connection between DNA and tRNA metabolism.
 ---
 
 # Dpd
diff --git a/content/2.defense-systems/gp29_gp30.md b/content/2.defense-systems/gp29_gp30.md
index efb24219..7a5b0937 100644
--- a/content/2.defense-systems/gp29_gp30.md
+++ b/content/2.defense-systems/gp29_gp30.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       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.
+        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.
 ---
 
 # gp29_gp30
diff --git a/content/2.defense-systems/lamassu-fam.md b/content/2.defense-systems/lamassu-fam.md
index dfbba4a1..edf177a6 100644
--- a/content/2.defense-systems/lamassu-fam.md
+++ b/content/2.defense-systems/lamassu-fam.md
@@ -105,7 +105,7 @@ Subsystem LmuB+LmuC+PDDEXK nuclease with a system from *Bacillus sp. UNCCL81* in
 
 Subsystem LmuA+LmuC+LmuB with a system from *Janthinobacterium agaricidamnosum* in *Escherichia coli* has an anti-phage effect against T1, T3, T7, LambdaVir, PVP-SE1 (Payne et al., 2021)
 
-Subsystem DdmABC with a system from *Vibrio cholerae* in *Escherichia coli* has an anti-phage effect against P1, Lambda (Jaskólska et al., 2022)
+Subsystem DdmABC with a system from *Vibrio cholerae* in *Escherichia coli* has an anti-phage effect against P1, Lambda (Jaskólska et al., 2022)
 
 ## Relevant abstracts
 
@@ -126,4 +126,4 @@ items:
 
 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
+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
diff --git a/content/2.defense-systems/mqsrac.md b/content/2.defense-systems/mqsrac.md
index 1596949a..934810f7 100644
--- a/content/2.defense-systems/mqsrac.md
+++ b/content/2.defense-systems/mqsrac.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1101/2023.02.25.529695
       abstract: |
-        Myriad bacterial anti-phage systems have been described and often the mechanism of programmed cell death is invoked for phage inhibition. However, there is little evidence of ‘suicide’ under physiological conditions for these systems. Instead of death to stop phage propagation, we show here that persister cells, i.e., transiently-tolerant, dormant, antibiotic-insensitive cells, are formed and survive using the Escherichia coli C496_10 tripartite toxin/antitoxin system MqsR/MqsA/MqsC to inhibit T2 phage. Specifically, MqsR/MqsA/MqsC inhibited T2 phage by one million-fold and reduced T2 titers by 500-fold. During T2 phage attack, in the presence of MqsR/MqsA/MqsC, evidence of persistence include the single-cell physiological change of reduced metabolism (via flow cytometry), increased spherical morphology (via transmission electron microscopy), and heterogeneous resuscitation. Critically, we found restriction-modification systems (primarily EcoK McrBC) work in concert with the toxin/antitoxin system to inactivate phage, likely while the cells are in the persister state. Phage attack also induces persistence in Klebsiella and Pseudomonas spp. Hence, phage attack invokes a stress response similar to antibiotics, starvation, and oxidation, which leads to persistence, and this dormant state likely allows restriction/modification systems to clear phage DNA.
+        Myriad bacterial anti-phage systems have been described and often the mechanism of programmed cell death is invoked for phage inhibition. However, there is little evidence of ‘suicide’ under physiological conditions for these systems. Instead of death to stop phage propagation, we show here that persister cells, i.e., transiently-tolerant, dormant, antibiotic-insensitive cells, are formed and survive using the Escherichia coli C496_10 tripartite toxin/antitoxin system MqsR/MqsA/MqsC to inhibit T2 phage. Specifically, MqsR/MqsA/MqsC inhibited T2 phage by one million-fold and reduced T2 titers by 500-fold. During T2 phage attack, in the presence of MqsR/MqsA/MqsC, evidence of persistence include the single-cell physiological change of reduced metabolism (via flow cytometry), increased spherical morphology (via transmission electron microscopy), and heterogeneous resuscitation. Critically, we found restriction-modification systems (primarily EcoK McrBC) work in concert with the toxin/antitoxin system to inactivate phage, likely while the cells are in the persister state. Phage attack also induces persistence in Klebsiella and Pseudomonas spp. Hence, phage attack invokes a stress response similar to antibiotics, starvation, and oxidation, which leads to persistence, and this dormant state likely allows restriction/modification systems to clear phage DNA.
 ---
 
 # MqsRAC
diff --git a/content/2.defense-systems/nixi.md b/content/2.defense-systems/nixi.md
index 5daf3baa..0befa10a 100644
--- a/content/2.defense-systems/nixi.md
+++ b/content/2.defense-systems/nixi.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1101/2021.07.12.452122
       abstract: |
-        PLEs are phage parasites integrated into the chromosome of epidemic Vibrio cholerae. In response to infection by its viral host ICP1, PLE excises, replicates and hijacks ICP1 structural components for transduction. Through an unknown mechanism PLE prevents ICP1 from transitioning to rolling circle replication (RCR), a prerequisite for efficient packaging of the viral genome. Here, we characterize a PLE-encoded nuclease, NixI, that blocks phage development likely by nicking ICP1Â’s genome as it transitions to RCR. NixI-dependent cleavage sites appear in ICP1Â’s genome during infection of PLE(+) V. cholerae. Purified NixI demonstrates in vitro specificity for sites in ICP1Â’s genome and NixI activity is enhanced by a putative specificity determinant co-expressed with NixI during phage infection. Importantly, NixI is sufficient to limit ICP1 genome replication and eliminate progeny production. We identify distant NixI homologs in an expanded family of putative phage satellites in Vibrios that lack nucleotide homology to PLEs but nonetheless share genomic synteny with PLEs. More generally, our results reveal a previously unknown mechanism deployed by phage parasites to limit packaging of their viral hostsÂ’ genome and highlight the prominent role of nuclease effectors as weapons in the arms race between antagonizing genomes.
+        PLEs are phage parasites integrated into the chromosome of epidemic Vibrio cholerae. In response to infection by its viral host ICP1, PLE excises, replicates and hijacks ICP1 structural components for transduction. Through an unknown mechanism PLE prevents ICP1 from transitioning to rolling circle replication (RCR), a prerequisite for efficient packaging of the viral genome. Here, we characterize a PLE-encoded nuclease, NixI, that blocks phage development likely by nicking ICP1’s genome as it transitions to RCR. NixI-dependent cleavage sites appear in ICP1’s genome during infection of PLE(+) V. cholerae. Purified NixI demonstrates in vitro specificity for sites in ICP1’s genome and NixI activity is enhanced by a putative specificity determinant co-expressed with NixI during phage infection. Importantly, NixI is sufficient to limit ICP1 genome replication and eliminate progeny production. We identify distant NixI homologs in an expanded family of putative phage satellites in Vibrios that lack nucleotide homology to PLEs but nonetheless share genomic synteny with PLEs. More generally, our results reveal a previously unknown mechanism deployed by phage parasites to limit packaging of their viral hosts’ genome and highlight the prominent role of nuclease effectors as weapons in the arms race between antagonizing genomes.
     Sensor: Unknown
     Activator: Unknown
     Effector: Nucleic acid degrading
diff --git a/content/2.defense-systems/pago.md b/content/2.defense-systems/pago.md
index 367efb94..eae65575 100644
--- a/content/2.defense-systems/pago.md
+++ b/content/2.defense-systems/pago.md
@@ -7,8 +7,7 @@ tableColumns:
         BACKGROUND: In eukaryotes, RNA interference (RNAi) is a major mechanism of defense against viruses and transposable elements as well of regulating translation of endogenous mRNAs. The RNAi systems recognize the target RNA molecules via small guide RNAs that are completely or partially complementary to a region of the target. Key components of the RNAi systems are proteins of the Argonaute-PIWI family some of which function as slicers, the nucleases that cleave the target RNA that is base-paired to a guide RNA. Numerous prokaryotes possess the CRISPR-associated system (CASS) of defense against phages and plasmids that is, in part, mechanistically analogous but not homologous to eukaryotic RNAi systems. Many prokaryotes also encode homologs of Argonaute-PIWI proteins but their functions remain unknown. RESULTS: We present a detailed analysis of Argonaute-PIWI protein sequences and the genomic neighborhoods of the respective genes in prokaryotes. Whereas eukaryotic Ago/PIWI proteins always contain PAZ (oligonucleotide binding) and PIWI (active or inactivated nuclease) domains, the prokaryotic Argonaute homologs (pAgos) fall into two major groups in which the PAZ domain is either present or absent. The monophyly of each group is supported by a phylogenetic analysis of the conserved PIWI-domains. Almost all pAgos that lack a PAZ domain appear to be inactivated, and the respective genes are associated with a variety of predicted nucleases in putative operons. An additional, uncharacterized domain that is fused to various nucleases appears to be a unique signature of operons encoding the short (lacking PAZ) pAgo form. By contrast, almost all PAZ-domain containing pAgos are predicted to be active nucleases. Some proteins of this group (e.g., that from Aquifex aeolicus) have been experimentally shown to possess nuclease activity, and are not typically associated with genes for other (putative) nucleases. Given these observations, the apparent extensive horizontal transfer of pAgo genes, and their common, statistically significant over-representation in genomic neighborhoods enriched in genes encoding proteins involved in the defense against phages and/or plasmids, we hypothesize that pAgos are key components of a novel class of defense systems. The PAZ-domain containing pAgos are predicted to directly destroy virus or plasmid nucleic acids via their nuclease activity, whereas the apparently inactivated, PAZ-lacking pAgos could be structural subunits of protein complexes that contain, as active moieties, the putative nucleases that we predict to be co-expressed with these pAgos. All these nucleases are predicted to be DNA endonucleases, so it seems most probable that the putative novel phage/plasmid-defense system targets phage DNA rather than mRNAs. Given that in eukaryotic RNAi systems, the PAZ domain binds a guide RNA and positions it on the complementary region of the target, we further speculate that pAgos function on a similar principle (the guide being either DNA or RNA), and that the uncharacterized domain found in putative operons with the short forms of pAgos is a functional substitute for the PAZ domain. CONCLUSION: The hypothesis that pAgos are key components of a novel prokaryotic immune system that employs guide RNA or DNA molecules to degrade nucleic acids of invading mobile elements implies a functional analogy with the prokaryotic CASS and a direct evolutionary connection with eukaryotic RNAi. The predictions of the hypothesis including both the activities of pAgos and those of the associated endonucleases are readily amenable to experimental tests.
     Sensor: Detecting invading nucleic acid
     Activator: Direct
-    Effector: Diverse (Nucleotide modifying 
-Membrane disrupting)
+    Effector: Diverse (Nucleotide modifyingn, Membrane disrupting)
 ---
 
 # pAgo
diff --git a/content/2.defense-systems/pycsar.md b/content/2.defense-systems/pycsar.md
index 96c61b1c..1bbf925f 100644
--- a/content/2.defense-systems/pycsar.md
+++ b/content/2.defense-systems/pycsar.md
@@ -7,8 +7,7 @@ tableColumns:
         The cyclic pyrimidines 3',5'-cyclic cytidine monophosphate (cCMP) and 3',5'-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria.
     Sensor: Unknown
     Activator: Signaling molecules
-    Effector: Membrane disrupting
-Nucleotides modifying
+    Effector: Membrane disrupting, Nucleotides modifying
 ---
 
 # Pycsar
diff --git a/content/2.defense-systems/radar.md b/content/2.defense-systems/radar.md
index 06afd1ec..191d0d51 100644
--- a/content/2.defense-systems/radar.md
+++ b/content/2.defense-systems/radar.md
@@ -68,4 +68,4 @@ items:
 
 ## References
 
-1. Gao L, Altae-Tran H, Böhning F, et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. *Science*. 2020;369(6507):1077-1084. doi:10.1126/science.aba0372
+1. Gao L, Altae-Tran H, Böhning F, et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. *Science*. 2020;369(6507):1077-1084. doi:10.1126/science.aba0372
diff --git a/content/2.defense-systems/rnlab.md b/content/2.defense-systems/rnlab.md
index bfada7e1..c011da5f 100644
--- a/content/2.defense-systems/rnlab.md
+++ b/content/2.defense-systems/rnlab.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1534/genetics.110.121798
       abstract: |
-        RNase LS was originally identified as a potential antagonist of bacteriophage T4 infection. When T4 dmd is defective, RNase LS activity rapidly increases after T4 infection and cleaves T4 mRNAs to antagonize T4 reproduction. Here we show that rnlA, a structural gene of RNase LS, encodes a novel toxin, and that rnlB (formally yfjO), located immediately downstream of rnlA, encodes an antitoxin against RnlA. Ectopic expression of RnlA caused inhibition of cell growth and rapid degradation of mRNAs in ?rnlAB cells. On the other hand, RnlB neutralized these RnlA effects. Furthermore, overexpression of RnlB in wild-type cells could completely suppress the growth defect of a T4 dmd mutant, that is, excess RnlB inhibited RNase LS activity. Pull-down analysis showed a specific interaction between RnlA and RnlB. Compared to RnlA, RnlB was extremely unstable, being degraded by ClpXP and Lon proteases, and this instability may increase RNase LS activity after T4 infection. All of these results suggested that rnlA–rnlB define a new toxin–antitoxin (TA) system.
+        RNase LS was originally identified as a potential antagonist of bacteriophage T4 infection. When T4 dmd is defective, RNase LS activity rapidly increases after T4 infection and cleaves T4 mRNAs to antagonize T4 reproduction. Here we show that rnlA, a structural gene of RNase LS, encodes a novel toxin, and that rnlB (formally yfjO), located immediately downstream of rnlA, encodes an antitoxin against RnlA. Ectopic expression of RnlA caused inhibition of cell growth and rapid degradation of mRNAs in ?rnlAB cells. On the other hand, RnlB neutralized these RnlA effects. Furthermore, overexpression of RnlB in wild-type cells could completely suppress the growth defect of a T4 dmd mutant, that is, excess RnlB inhibited RNase LS activity. Pull-down analysis showed a specific interaction between RnlA and RnlB. Compared to RnlA, RnlB was extremely unstable, being degraded by ClpXP and Lon proteases, and this instability may increase RNase LS activity after T4 infection. All of these results suggested that rnlA–rnlB define a new toxin–antitoxin (TA) system.
     Sensor: Monitor the integrity of the bacterial cell machinery
     Activator: Direct
     Effector: Nucleic acid degrading
diff --git a/content/2.defense-systems/sefir.md b/content/2.defense-systems/sefir.md
index dc1f1486..e299110e 100644
--- a/content/2.defense-systems/sefir.md
+++ b/content/2.defense-systems/sefir.md
@@ -59,4 +59,4 @@ items:
 
 ## References
 [1] Millman, A. et al. An expanded arsenal of immune systems that protect bacteria from phages. Cell Host Microbe 30, 1556-1569.e5 (2022).
-[2] Novatchkova, M., Leibbrandt, A., Werzowa, J., Neubüser, A., & Eisenhaber, F. (2003). The STIR-domain superfamily in signal transduction, development and immunity. _Trends in biochemical sciences_, _28_(5), 226-229.
+[2] Novatchkova, M., Leibbrandt, A., Werzowa, J., Neubüser, A., & Eisenhaber, F. (2003). The STIR-domain superfamily in signal transduction, development and immunity. _Trends in biochemical sciences_, _28_(5), 226-229.
diff --git a/content/2.defense-systems/shango.md b/content/2.defense-systems/shango.md
index 76a3b0e1..399734e0 100644
--- a/content/2.defense-systems/shango.md
+++ b/content/2.defense-systems/shango.md
@@ -63,7 +63,7 @@ items:
 ## References
 Shango was discovered in parallel by Adi Millman (Sorek group) and the team of J. Bondy-Denomy (UCSF). 
 
-[1] Millman, A., Melamed, S., Leavitt, A., Doron, S., Bernheim, A., Hör, J., Garb, J., Bechon, N., Brandis, A., Lopatina, A., Ofir, G., Hochhauser, D., Stokar-Avihail, A., Tal, N., Sharir, S., Voichek, M., Erez, Z., Ferrer, J. L. M., Dar, D., … Sorek, R. (2022). An expanded arsenal of immune systems that protect bacteria from phages. _Cell Host & Microbe_, _30_(11), 1556-1569.e5. [https://doi.org/10.1016/j.chom.2022.09.017](https://doi.org/10.1016/j.chom.2022.09.017)
+[1] Millman, A., Melamed, S., Leavitt, A., Doron, S., Bernheim, A., Hör, J., Garb, J., Bechon, N., Brandis, A., Lopatina, A., Ofir, G., Hochhauser, D., Stokar-Avihail, A., Tal, N., Sharir, S., Voichek, M., Erez, Z., Ferrer, J. L. M., Dar, D., … Sorek, R. (2022). An expanded arsenal of immune systems that protect bacteria from phages. _Cell Host & Microbe_, _30_(11), 1556-1569.e5. [https://doi.org/10.1016/j.chom.2022.09.017](https://doi.org/10.1016/j.chom.2022.09.017)
 
 [2] Johnson, Matthew, Laderman, Eric, Huiting, Erin, Zhang, Charles, Davidson, Alan, & Bondy-Denomy, Joseph. (2022). _Core Defense Hotspots within Pseudomonas aeruginosa are a consistent and rich source of anti-phage defense systems_. [https://doi.org/10.5281/ZENODO.7254690](https://doi.org/10.5281/ZENODO.7254690)
 
diff --git a/content/2.defense-systems/spbk.md b/content/2.defense-systems/spbk.md
index 2869557f..d7b93c17 100644
--- a/content/2.defense-systems/spbk.md
+++ b/content/2.defense-systems/spbk.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1371/journal.pgen.1010065
       abstract: |
-        Most bacterial genomes contain horizontally acquired and transmissible mobile genetic elements, including temperate bacteriophages and integrative and conjugative elements. Little is known about how these elements interact and co-evolved as parts of their host genomes. In many cases, it is not known what advantages, if any, these elements provide to their bacterial hosts. Most strains of Bacillus subtilis contain the temperate phage SPß and the integrative and conjugative element ICEBs1. Here we show that the presence of ICEBs1 in cells protects populations of B. subtilis from predation by SPß, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SPß killing) was both necessary and sufficient for this protection. spbK inhibited production of SPß, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SPß gene yonE constitutes an abortive infection system that leads to cell death. spbK encodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to some plant antiviral proteins and animal innate immune signaling proteins. We postulate that many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements.
+        Most bacterial genomes contain horizontally acquired and transmissible mobile genetic elements, including temperate bacteriophages and integrative and conjugative elements. Little is known about how these elements interact and co-evolved as parts of their host genomes. In many cases, it is not known what advantages, if any, these elements provide to their bacterial hosts. Most strains of Bacillus subtilis contain the temperate phage SPß and the integrative and conjugative element ICEBs1. Here we show that the presence of ICEBs1 in cells protects populations of B. subtilis from predation by SPß, likely providing selective pressure for the maintenance of ICEBs1 in B. subtilis. A single gene in ICEBs1 (yddK, now called spbK for SPß killing) was both necessary and sufficient for this protection. spbK inhibited production of SPß, during both activation of a lysogen and following de novo infection. We found that expression spbK, together with the SPß gene yonE constitutes an abortive infection system that leads to cell death. spbK encodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to some plant antiviral proteins and animal innate immune signaling proteins. We postulate that many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements.
     Sensor: Unknown
     Activator: Unknown
     Effector: Unknown
diff --git a/content/2.defense-systems/viperin.md b/content/2.defense-systems/viperin.md
index be3827d5..8bf85a84 100644
--- a/content/2.defense-systems/viperin.md
+++ b/content/2.defense-systems/viperin.md
@@ -4,7 +4,7 @@ tableColumns:
     article:
       doi: 10.1038/s41586-020-2762-2
       abstract: |
-        Viperin is an interferon-induced cellular protein that is conserved in animals1. 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.
+        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
     Effector: Nucleotide modifying
@@ -14,7 +14,7 @@ tableColumns:
 # 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 (1).  
 
 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).
 
@@ -23,7 +23,7 @@ Recently,  Viperin-like enzymes were found in prokaryotes (pVips).  Strikingly
 
 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) (4,5). 
 
 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).
 
-- 
GitLab