Phage gene expression and host responses lead to infection-dependent costs of CRISPR immunity

• Published in: The ISME Journal Vol. 15; no. 2; pp. 534 - 544
• Main Authors: Meaden, Sean, Capria, Loris, Alseth, Ellinor, Gandon, Sylvain, Biswas, Ambarish, Lenzi, Luca, van Houte, Stineke, Westra, Edze R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2021; Nature Publishing Group
• Subjects: 38/91; 45/23; 631/326/1321; 704/158/855; Adaptive immunology; Archaea; Autoimmunity; Bacteria; Bacteriology; Bacteriophages - genetics; Biomedical and Life Sciences; Cellular apoptosis susceptibility protein; Cleavage; Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR; CRISPR-Cas Systems; Ecology; Evolutionary Biology; Fitness; Gene Expression; Genes; Genomes; Immune system; Immunity; Immunology; Infections; Life Sciences; Microbial Ecology; Microbial Genetics and Genomics; Microbiology; Microbiology and Parasitology; Mutation; Phages; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Reproductive fitness; Toxicity
• ISSN: 1751-7362; 1751-7370
• DOI: 10.1038/s41396-020-00794-w

CRISPR-Cas immune systems are widespread in bacteria and archaea, but not ubiquitous. Previous work has demonstrated that CRISPR immunity is associated with an infection-induced fitness cost, which may help explain the patchy distribution observed. However, the mechanistic basis of this cost has remained unclear. Using Pseudomonas aeruginosa PA14 and its phage DMS3vir as a model, we perform a 30-day evolution experiment under phage mediated selection. We demonstrate that although CRISPR is initially selected for, bacteria carrying mutations in the phage receptor rapidly invade the population following subsequent reinfections. We then test three potential mechanisms for the observed cost of CRISPR: (1) autoimmunity from the acquisition of self-targeting spacers, (2) immunopathology or energetic costs from increased cas gene expression and (3) toxicity caused by phage gene expression prior to CRISPR-mediated cleavage. We find that phages can express genes before the immune system clears the infection and that expression of these genes can have a negative effect on host fitness. While infection does not lead to increased expression of cas genes, it does cause differential expression of multiple other host processes that may further contribute to the cost of CRISPR immunity. In contrast, we found little support for infection-induced autoimmunological and immunopathological effects. Phage gene expression prior to cleavage of the genome by the CRISPR-Cas immune system is therefore the most parsimonious explanation for the observed phage-induced fitness cost.