Sedentary chromosomal integrons as biobanks of bacterial anti-phage defence systems

Integrons are genetic systems that accelerate bacterial adaptation by acquiring and shuffling gene cassettes. Mobile integrons spread antibiotic resistance genes among bacteria, while the sedentary chromosomal integrons contain up to hundreds of cassettes of unknown function. Here, we show that many of these cassettes encode anti-phage defence systems. We found numerous streamlined variants of known systems, which have presumably evolved to fit the small size constraints of integron cassettes recombination and genesis. Intrigued by the rarity of known systems in the sedentary chromosomal integron of the Vibrio cholerae 7th cholera pandemic strain, we tested the presence of anti-phage functions in all its cassettes of unknown function. We found that at least 16 of the strain cassettes have an anti-phage activity in V. cholerae or E. coli. This represents 18% of the tested cassettes and almost 10% of all the integron cassettes, providing at long last a key adaptive role for a significant fraction of the sedentary integrons. Most of the newly discovered systems have little or no similarity to previously known ones and our experiments show that several mediate defence through cell lysis or growth arrest. One of these systems encodes a 64 amino acids protein, which represents the smallest known protein providing autonomous phage resistance. Given the thousands of uncharacterized integron cassette families, integrons could represent an untapped treasure trove of streamlined anti-phage systems.