diff --git a/content/3.defense-systems/thoeris.md b/content/3.defense-systems/thoeris.md index 8efc711465b09e28993503d0994483eed18157ae..d67218adaad778bb9f5c04381c42e664467970df 100644 --- a/content/3.defense-systems/thoeris.md +++ b/content/3.defense-systems/thoeris.md @@ -7,12 +7,35 @@ tableColumns: abstract: | The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. Sensor: Unknown - Activator: Signaling + Activator: Signaling system Effector: Nucleotide modifying PFAM: PF08937, PF13289, PF18185 + +contributors: + - Marie Guillaume, Helena Shomar +relevantAbstracts: + - doi: 10.1038/s41586-021-04098-7 + - doi: 10.1126/science.aar4120 + - doi: 10.1038/s41467-020-16703-w + --- # Thoeris + +## Description +Thoeris is a two-gene defense system identified in more than 2000 bacterial genomes. It consists of the genes thsA and thsB. Its anti-phage function was experimentally validated in _Bacillus subtilis_. In response to phage infection, it produces an isomer of cyclic ADP-ribose, which leads to depletion of NAD+ and results in abortive infection. + +ThsA contains the sirtuin-like domain which binds to nicotinamide adenine dinucleotide (NAD) metabolites. The N112A point mutation neutralizes the Thoeris defense system and abolishes the NAD+ hydrolase activity of thsA. It lacks a N-terminal transmembrane domain, and is predicted to be cytoplasmic. + +ThsB is proposed to participate in the recognition of phage infection, as various thsB proteins sense different phage components.ThsB is found in more than 50% of Thoeris systems in multiple diverse copies. + + +## Molecular mechanism + +The Thoeris system is believed to function by degrading NAD+ (a cofactor of central metabolism) to stop the growth of phage-infected cells and prevent the transmission of the phage to neighboring bacteria. + +The protein ThsB, featuring the TIR domain, plays a cruial role in identifying phage invasion. Upon detecting the infection, the TIR domain becomes enzymatically active, initiating the synthesis of a cADPR isomer molecule. This molecule acts as a signal, binding to the ThsA effector, likely through its C-terminal SLOG domain, thereby activating its NADase activity. Consequently, the NADase effector reduces NAD+ cellular levels, creating an environment unsuitable for phage replication. + ## Example of genomic structure The Thoeris system have been describe in a total of 2 subsystems. @@ -130,14 +153,4 @@ end style Title3 fill:none,stroke:none,stroke-width:none style Title4 fill:none,stroke:none,stroke-width:none </mermaid> -## Relevant abstracts - -::relevant-abstracts ---- -items: - - doi: 10.1038/s41586-021-04098-7 - - doi: 10.1126/science.aar4120 - ---- -::