Bacterial defences interact synergistically by disrupting phage cooperation

Maestri, A.; Pursey, E.; Chong, C.; Pons, B. J.; Gandon, S.; Custodio, R.; Chisnall, M.; Grasso, A.; Paterson, S.; Baker, K. S.; van Houte, S.; Chevallereau, A.; Westra, E.

doi:10.1101/2023.03.30.534895

bioRxiv · 10.1101/2023.03.30.534895

Bacterial defences interact synergistically by disrupting phage cooperation

Maestri, A.·Pursey, E.·Chong, C.·Pons, B. J.·Gandon, S.·Custodio, R.·Chisnall, M.·Grasso, A.·Paterson, S.·Baker, K. S.·van Houte, S.·Chevallereau, A.·Westra, E.

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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.

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Maestri, A., Pursey, E., Chong, C., Pons, B. J., Gandon, S., Custodio, R., Chisnall, M., Grasso, A., Paterson, S., Baker, K. S., van Houte, S., Chevallereau, A., Westra, E.. 2023-03-30. Bacterial defences interact synergistically by disrupting phage cooperation. https://doi.org/10.1101/2023.03.30.534895

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