mads.md

title: MADS
layout: article
tableColumns:
    article:
      doi: 10.1101/2023.03.30.534895
      abstract: |
        The constant arms race between bacteria and their phages has resulted in a large diversity of bacterial defence systems1,2, with many bacteria carrying several systems3,4. In response, phages often carry counter-defence genes5-9. If and how bacterial defence mechanisms interact to protect against phages with counter-defence genes remains unclear. Here, we report the existence of a novel defence system, coined MADS (Methylation Associated Defence System), which is located in a strongly conserved genomic defence hotspot in Pseudomonas aeruginosa and distributed across Gram-positive and Gram-negative bacteria. We find that the natural co-existence of MADS and a Type IE CRISPR-Cas adaptive immune system in the genome of P. aeruginosa SMC4386 provides synergistic levels of protection against phage DMS3, which carries an anti-CRISPR (acr) gene. Previous work has demonstrated that Acr-phages need to cooperate to overcome CRISPR immunity, with a first sacrificial phage causing host immunosuppression to enable successful secondary phage infections10,11. Modelling and experiments show that the co-existence of MADS and CRISPR-Cas provides strong and durable protection against Acr-phages by disrupting their cooperation and limiting the spread of mutants that overcome MADS. These data reveal that combining bacterial defences can robustly neutralise phage with counter-defence genes, even if each defence on its own can be readily by-passed, which is key to understanding how selection acts on defence combinations and their coevolutionary consequences.
    PFAM: PF00069, PF01170, PF02384, PF07714, PF08378, PF12728, PF13304, PF13588

MADS

To do

Example of genomic structure

The MADS is composed of 8 proteins: mad1, mad2, mad3, mad4, mad5, mad6, mad7 and mad8.

Here is an example found in the RefSeq database:

The MADS system in Pseudomonas otitidis (GCF_019879085.1, NZ_CP082244) is composed of 8 proteins mad1 (WP_058876992.1) mad2 (WP_208273447.1) mad3 (WP_208273444.1) mad4 (WP_208273442.1) mad5 (WP_208273440.1) mad6 (WP_208273438.1) mad7 (WP_208273430.1) mad8 (WP_233473447.1)

Distribution of the system among prokaryotes

Among the 22,803 complete genomes of RefSeq, the MADS is detected in 72 genomes (0.32 %).

The system was detected in 63 different species.

Proportion of genome encoding the MADS system for the 14 phyla with more than 50 genomes in the RefSeq database.

Structure

MADS

::molstar-pdbe-plugin

height: 700 dataUrl: /mads/MADS__mad1-plddts_82.3118.pdb

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height: 700 dataUrl: /mads/MADS__mad2-plddts_87.54253.pdb

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height: 700 dataUrl: /mads/MADS__mad3-plddts_93.27207.pdb

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::molstar-pdbe-plugin

height: 700 dataUrl: /mads/MADS__mad4-plddts_92.44061.pdb

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::molstar-pdbe-plugin

height: 700 dataUrl: /mads/MADS__mad5-plddts_93.90587.pdb

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::molstar-pdbe-plugin

height: 700 dataUrl: /mads/MADS__mad7-plddts_91.54141.pdb

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height: 700 dataUrl: /mads/MADS__mad8-plddts_82.23514.pdb

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Experimental validation

graph LR; Maestri_2023[Maestri et al., 2023] --> Origin_0 Origin_0[Pseudomonas aeruginosa WP_058876987.1, WP_058876988.1, WP_058876989.1, WP_058876990.1, WP_058876991.1, WP_058876992.1, WP_124170283.1, WP_201267341.1] --> Expressed_0[Pseudomonas aeruginosa] Expressed_0[Pseudomonas aeruginosa] ----> DMS3vir subgraph Title1[Reference] Maestri_2023 end subgraph Title2[System origin] Origin_0 end subgraph Title3[Expression species] Expressed_0 end subgraph Title4[Phage infected] DMS3vir end style Title1 fill:none,stroke:none,stroke-width:none style Title2 fill:none,stroke:none,stroke-width:none style Title3 fill:none,stroke:none,stroke-width:none style Title4 fill:none,stroke:none,stroke-width:none ## Relevant abstract ::relevant-abstracts --- items: - doi: 10.1101/2023.03.30.534895

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