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Integrons are goldmines of anti-phage defense systems
Baptiste Darracq  1, 2@  , Eloi Littner  3, 4  , Florence Depardieu  5  , Julia Bos  1  , Manon Brunie  1  , David Bikard  5  , Didier Mazel  1  , Frédérique Le Roux  6  , Eduardo Rocha  3  , Céline Loot  1  
1 : Plasticité du Génome Bactérien - Bacterial Genome Plasticity
Institut Pasteur [Paris], Centre National de la Recherche Scientifique, Université Paris Cité
Département Génomes et Génétique - 25-28, rue du docteur Roux, 75724 Paris Cedex 15 -  France
2 : ED 515 - Complexité du vivant
Sorbonne Université
7 Quai Saint-Bernard 75005 Paris -  France
3 : Génomique évolutive des Microbes / Microbial Evolutionary Genomics
Institut Pasteur [Paris], Centre National de la Recherche Scientifique, Université Paris Cité
Département Génomes et Génétique - 25-28 rue du docteur Roux, F-75724 Paris Cedex 15 -  France
4 : Centre d'Études du Bouchet
Délégation Générale pour l'Armement
3 rue Lavoisier BP 3 91710 Vert-le-Petit -  France
5 : Biologie de Synthèse - Synthetic biology
Université Paris Cité, Microbiologie Intégrative et Moléculaire
Département Microbiologie, 25-28 rue du Docteur Roux, 75724 Paris Cedex 15 -  France
6 : CRSN/Faculté de médecine Université de Montréal
CRSN/Faculté de médecine Université de Montréal Pav. Paul-G.-Desmarais, 4139 or 2140 2960, chemin de la Tour Montréal (Québec) H3T 1J4 -  Canada

Integrons are genetic platforms that allow bacteria to adapt to different environmental stressors through the acquisition of new genes embedded into cassettes. These systems work by capturing, storing and rearranging cassettes, which ensures the exploration of diverse phenotypic combinations as only the first cassettes of the integron are expressed [1]. While integrons are best known for their role in antibiotic resistance, up to several hundred uncharacterised cassettes can be found in large integrons. Given the plasticity of these adaptation on demand platforms, in this work we set out to explore the role of the cassettes present in the Vibrio cholerae chromosomal integron as defence systems against phages. Through the overexpression of 88 of these cassettes, we found that 16 displayed anti-phage activity in either V. cholerae or E. coli. We also showed that these usually silent cassettes can be mobilized and expressed by the integron and thus confer resistance to phages in their natural genetic context. Most of the systems encoded in these cassettes have little or no similarity to previously known ones. Moreover, they exhibit typical features of abortive infection behavior, in which the defense system targets its host cell after detecting the presence of the phage, preventing viral amplification and protecting the rest of the population [2]. With these results, we confirm the propensity of integrons to be hotspots for anti-phage systems at a low cost for the cells.

[1] Escudero, Loot, Nivina and Mazel, Microbiol Spectr, Mar. 2015

[2] Yen et al., Nat. Commun., Feb. 2017


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