fix typos

content/2.general-concepts/0.index.md

@@ -9,11 +9,11 @@ In the following pages are presented different general concepts that are useful
 
 You'll find information on :
 
-1. [Abortive infection](/general-concepts/abortive-infection/)
-2. [Defense Islands  ](/general-concepts/defense-islands/)
-3. [Triggers of defense systems](/general-concepts/defense-systems_trigger/)
-4. [Effectors of defense systems](/general-concepts/defense-systems_effector/)
-5. [How defense systems were and are discovered](/general-concepts/defense-systems-discovery/)
+1. [Abortive infection](/general-concepts/abortive-infection)
+2. [Defense Islands](/general-concepts/defense-islands)
+3. [Triggers of defense systems](/general-concepts/defense-systems_trigger)
+4. [Effectors of defense systems](/general-concepts/defense-systems_effector)
+5. [How defense systems were and are discovered](/general-concepts/defense-systems-discovery)
 6. [Defensive domains](/general-concepts/defensive-domains/)
 7. [MGE and defense systems](/general-concepts/mge-defense-systems/)
 8. [Anti defense systems](/general-concepts/anti-defense-systems/)
\ No newline at end of file

content/2.general-concepts/2.defense-islands.md

@@ -11,8 +11,8 @@ contributors:
 
 # Defense Islands
 
-**Defense islands** are regions of prokaryotic genomes enriched in defense systems. Their existence first described in Makarova *et al.*:ref{doi=10.1128/JB.05535-11}, who observed that genes encoding defense systems (mainly Restriction Modification enzymes, Toxin-Antitoxin systems, but notably not CRISPR) tended to cluster preferentially on specific portions of bacterial genomes. They postulated that unknown genes commonly found associated to these regions would likely have a defensive role themselves, and confirmed bioinformatically that many of them were indeed diverged versions of classical defense systems. Other systems of genes commonly found in defense islands were later isolated and heterologously expressed to experimentally confirm to have a defensive role (BREX, DISARM). Doron *et al.*:ref{10.1126/science.aar4120}, later followed by Millmann *et al.*:ref{https://doi.org/10.1016/j.chom.2022.09.017}, used the colocalization of genes in defense islands to generate many candidate systems and test them experimentally in high throughput screens, leading to the discovery of a large number of new defense systems.
+**Defense islands** are regions of prokaryotic genomes enriched in defense systems. Their existence first described in Makarova *et al.* :ref{doi=10.1128/JB.05535-11}, who observed that genes encoding defense systems (mainly Restriction Modification enzymes, Toxin-Antitoxin systems, but notably not CRISPR) tended to cluster preferentially on specific portions of bacterial genomes. They postulated that unknown genes commonly found associated to these regions would likely have a defensive role themselves, and confirmed bioinformatically that many of them were indeed diverged versions of classical defense systems. Other systems of genes commonly found in defense islands were later isolated and heterologously expressed to experimentally confirm to have a defensive role (BREX, DISARM). Doron *et al.* :ref{doi=10.1126/science.aar4120}, later followed by Millmann *et al.* :ref{doi=10.1016/j.chom.2022.09.017}, used the colocalization of genes in defense islands to generate many candidate systems and test them experimentally in high throughput screens, leading to the discovery of a large number of new defense systems.
 
-The reasons leading to the formation and maintenance of defense islands are still unclear. Makarova *et al.*:ref{doi=10.1128/JB.05535-11} observed a that defense islands often associated with mobile genetic elements, suggesting that defense systems travel through horizontal gene transfer, taking advantage of the MGEs' mobility. This observation in itself could explain the non-random localization of defense systems in the preferred "landing pads" (=*sinks*) of mobile genetic elements. Whether the colocalization of defense systems into these islands is purely due to there horizontal transmission, or whether they reflect a deeper functional implication such as coregulation and coordination, remains debated.  
+The reasons leading to the formation and maintenance of defense islands are still unclear. Makarova *et al.* :ref{doi=10.1128/JB.05535-11} observed a that defense islands often associated with mobile genetic elements, suggesting that defense systems travel through horizontal gene transfer, taking advantage of the MGEs' mobility. This observation in itself could explain the non-random localization of defense systems in the preferred "landing pads" (=*sinks*) of mobile genetic elements. Whether the colocalization of defense systems into these islands is purely due to there horizontal transmission, or whether they reflect a deeper functional implication such as coregulation and coordination, remains debated.  
 
 

content/2.general-concepts/3.defense-systems_trigger.md

@@ -7,14 +7,18 @@ layout: article
 ---
 
 # How anti-phage systems sense invading phages
+
 Upon phage infection, the bacterial immune system senses a specific phage component or modification that the phage exerts on the cell to elicit the bacterial immune response. Understanding how bacteria sense phage infection is a fundamental question, which remains unanswered for the majority of recently discovered immune systems. There are dozens of cases in which the mechanism of immunity has been elucidated, but the phage trigger remains elusive. Understanding how antiphage systems are activated is key for a full understanding of bacterial immunity and for repurposing them as molecular tools as has been done for restriction enzymes and CRISPR-Cas. 
 
 ## Diversity
+
 Various determinants of the phage can elicit bacterial immunity either in a direct or indirect manner. The most common and well known prokaryotic anti-phage systems, restriction enzymes and CRISPR-Cas, recognize and cleave phage DNA or RNA. More recently, a CBASS system has been found to directly bind to a structured phage RNA that triggers immune activation :ref{doi=10.1101/2023.03.07.531596}. In other cases, defense systems are activated by protein coding phage genes. In some cases, the phage protein is directly sensed by the defense systems, as has been beautifully demonstrated for the Avs systems that directly bind either the phage terminase or portal protein :ref{doi=10.1126/science.abm4096}. In other cases, the phage protein can be sensed indirectly by the defense system, for example by detecting its activity in the cell. Such an indirect mechanism has been found for example in the case of some retron defense systems that are triggered by phage tampering with the RecBCD protein complex :ref{doi=10.1016/j.cell.2020.09.065,10.1016/j.cell.2023.02.029}. For a comprehensive coverage of all recent phage detection mechanisms the recent review by Huiting and Bondy-Denomy :ref{doi=10.1016/j.mib.2023.102325} is highly recommended. 
 
 ## Method of discovery:
+
 The main method used to pinpoint phage components that trigger a specific defense system of interest has been through a simple classic genetics approach, whereby mutant phages that overcome the defense system are examined. Such mutants often occur spontaneously and can thus be selected for by simply picking phage plaques that are able to form on a lawn of bacteria expressing the defense system :ref{doi=10.1016/j.cell.2023.02.029,10.1016/j.mib.2023.102325}. The hypothesis is that the phage mutant escapes bacterial immunity due to a mutation in the component sensed by the system. Thus, sequencing these phage mutants and identification of the mutated locus is the first required step. To validate that the mutated phage component is indeed the actual trigger of the defense system, follow up experiments are required. For example, in some cases expression of this phage component without any other phage genes is sufficient to elicit the activity of bacterial immune system. This approach was used to identify Borvo activation by expression of the phage DNA polymerase, Dazbog activation by expression of a phage DNA methylase, retron activation by either phage SSB proteins :ref{doi=10.1016/j.cell.2023.02.029} or by proteins that inhibit the host RecBCD3, CapRel triggering by the phage Capsid protein :ref{doi=10.1038/s41586-022-05444-z} and many more :ref{doi=10.1016/j.mib.2023.102325}. Additional biochemical pulldown assays can be used to assess binding of the defense system to the suspected phage trigger. 
 One major caveat in the above approach is that in some cases mutant phages that escape the immune system cannot be isolated. This can occur for example if the defense system senses a general fold of a highly conserved and essential phage protein. In this case a simple mutation in the protein will not suffice for the phage to escape detection. In such cases, an alternative approach can be used that does not rely on isolation of escape mutants. An overexpression library of all phage genes can be co-expressed with the defense system of interest, and then assayed for immune activation. This approach was successfully applied for identification phage components that trigger diverse Avs systems :ref{doi=10.1126/science.abm4096}. 
 
-## General concepts: 
+## General concepts
+
 Although much is still unknown regarding how bacterial immune systems sense phage infection, by combining the data observed so far, several general concepts in immune sensing are beginning to come to light. First, mechanistically diverse immune systems appear to have converged to sense common conserved phage components4.  These include the phage core replication machinery, host takeover machinery and structural components. Second, several studies have found cases in which defense occurs in a multi-layered fashion, whereby a second system is activated when the first one fails  :ref{doi=10.1016/j.cell.2020.09.065,10.1016/j.chom.2022.02.018,10.1006/jmbi.1995.0343}. Research in upcoming years is expected to reveal additional guiding principles in the ways bacteria detect phages. 

content/2.general-concepts/defense-systems-effectors.md

@@ -16,7 +16,7 @@ The effector components of anti-phage systems are very diverse, and can be arbit
 ## Nucleic-acid-degrading effectors.
 
 Many defense systems target (either through cleavage or modification) nucleic acids to mediate the immune response. These nucleic acids targeting systems are divided between systems that specifically target phage nucleic acids to stop phage replication, and systems that untargetedly affect bacterial and viral nucleic acids to halt the growth of both the infected host and the phage. 
-Nucleic-acid-degrading systems include [RM](/defense-systems/RM), [CRISPR-Cas](/defense-systems/Cas), [Ssp](defense-systems/sspbcde) and [Ddn](defense-systems/dnd), certain types of [CBASS](/defense-systems/cbass), [Avs](/defense-systems/avs) and [Lamassu](/defense-systems/lamassu-fam), [PrrC](/defense-systems/prrc), [RloC](/defense-systems/rloc)...
+Nucleic-acid-degrading systems include [RM](/defense-systems/rm), [CRISPR-Cas](/defense-systems/cas), [Ssp](/defense-systems/sspbcde) and [Ddn](/defense-systems/dnd), certain types of [CBASS](/defense-systems/cbass), [Avs](/defense-systems/avs) and [Lamassu](/defense-systems/lamassu-fam), [PrrC](/defense-systems/prrc), [RloC](/defense-systems/rloc)...
 
 ## Nucleotide-modifying effectors.
 
@@ -24,7 +24,7 @@ Other types of defense systems target the nucleotide pool of the infected cell.
 
 ## Membrane-disrupting effectors.
 
-Many defense systems encode proteins that disrupt the membrane integrity of the infected cell (by opening pores, targeting the membrane phospholipids or through transmembrane domains), leading to growth arrest. They include for instance bacterial Gasdermins, RexAB, Pif, [AbiZ](), certain types of [pAgo](/defense-systems/pago), [retrons](/defense-systems/retron), [CBASS](/defense-systems/cbass), [PYCSAR](/defense-systems/pycsar) and [Avs](/defense-systems/avs) systems.
+Many defense systems encode proteins that disrupt the membrane integrity of the infected cell (by opening pores, targeting the membrane phospholipids or through transmembrane domains), leading to growth arrest. They include for instance bacterial Gasdermins, RexAB, Pif, AbiZ, certain types of [pAgo](/defense-systems/pago), [retrons](/defense-systems/retron), [CBASS](/defense-systems/cbass), [PYCSAR](/defense-systems/pycsar) and [Avs](/defense-systems/avs) systems.
 
 ## Other types of effectors.