Bacterial defences interact synergistically by disrupting phage cooperation


Maestri, Alice ORCID: 0000-0002-2176-8831, Pursey, Elizabeth, Chong, Charlotte, Pons, Benoit ORCID: 0000-0002-9137-1047, Gandon, Sylvain, Custodio, Rafael, Chisnall, Matthew, Grasso, Anita, Paterson, Steve ORCID: 0000-0002-1307-2981, Baker, Kate ORCID: 0000-0001-5850-1949 et al (show 3 more authors) (2023) Bacterial defences interact synergistically by disrupting phage cooperation. [Preprint]

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Abstract

<h4>Summary</h4> The constant arms race between bacteria and their phages has resulted in a large diversity of bacterial defence systems 1,2 , with many bacteria carrying several systems 3,4 . In response, phages often carry counter-defence genes 5–9 . 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 infections 10,11 . 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.

Item Type: Preprint
Uncontrolled Keywords: 3107 Microbiology, 3207 Medical Microbiology, 32 Biomedical and Clinical Sciences, 31 Biological Sciences, Genetics, 2.2 Factors relating to the physical environment, Generic health relevance, Infection
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 04 Apr 2023 14:42
Last Modified: 28 Aug 2025 22:48
DOI: 10.1101/2023.03.30.534895
Open Access URL: https://doi.org/10.1101/2023.03.30.534895
Related Websites:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3169431
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