Type I CRISPR-Cas provides robust immunity but incomplete attenuation of phage-induced cellular stress

During infection, phages manipulate bacteria to redirect metabolism towards viral proliferation. To counteract phages, some bacteria employ CRISPR-Cas systems that provide adaptive immunity. While CRISPR-Cas mechanisms have been studied extensively, their effects on both the phage and the host during phage infection remains poorly understood. Here, we analysed the infection of Serratia by a siphovirus (JS26) and the transcriptomic response with, or without type I-E or I-F CRISPR-Cas immunity. In non-immune Serratia, phage infection altered bacterial metabolism by upregulating anaerobic respiration and amino acid biosynthesis genes, while flagella production was suppressed. Furthermore, phage proliferation required a late-expressed viral Cas4, which did not influence CRISPR adaptation. While type I-E and I-F immunity provided robust defence against phage infection, phage development still impacted the bacterial host. Moreover, DNA repair and SOS response pathways were upregulated during type I immunity. We also discovered that the type I-F system is controlled by a positive autoregulatory feedback loop that is activated upon phage targeting during type I-F immunity, leading to a controlled anti-phage response. Overall, our results provide new insight into phage-host dynamics and the impact of CRISPR immunity within the infected cell. RNA-seq study perfomed of Serratia WT, Serratia I-F BIM and Serratia I-E BIM during infection with bacteriopage JS26 (moi=50). Samples were taken prior to infection (uninfected control) and 5, 20 and 40 minutes post infection. For each strain, trancriptomic changes were evaluated between each infection time point (5, 20 nd 40 minutes post infection) in comparison to the uninfected control using the DESeq2 R/Bioconductor package (3.5.2) with a Wald test, followed by a Benjamini and Hochberg procedure. The experiement was perfromed in biological triplicate (37 samples in total).