The underlying data for all figures are provided in supporting information file S1 Data.įunding: This project was funded by the Microbiology Program of the Innovative Genomics Institute, Berkeley (to VKM, AMD, and APA). In addition, the complete data from RB-TnSeq experiments are deposited here. Supplementary Tables with complete CRISPRi data are deposited here. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: Sequencing data have been uploaded to the Sequence Read Archive under BioProject accession number PRJNA645443. The results of this study and future efforts to map the phage resistance landscape will lead to new insights into the coevolution of hosts and their phage, which can ultimately be used to design better phage therapeutic treatments and tools for precision microbiome engineering. Our systematic and high-throughput genetic workflow to characterize phage-host interaction determinants can be extended to diverse bacteria to generate datasets that allow predictive models of how phage-mediated selection will shape bacterial phenotype and evolution. Our results indicate that host responses to phages can occur via diverse cellular mechanisms. We also identify both phage-specific mechanisms, such as the unexpected role of cyclic-di-GMP in host sensitivity to phage N4, and more generic defenses, such as the overproduction of colanic acid capsular polysaccharide that defends against a wide array of phages. We uncover differences in resistance factors that strongly align with the susceptibility of K-12 and BL21 to specific phage. Using genome-wide loss-of-function and gain-of-function genetic technologies, we are able to confirm previously described phage receptors as well as uncover a number of previously unknown host factors that confer resistance to one or more of these phages. Here, we globally map the host genetic determinants involved in resistance to 14 phylogenetically diverse double-stranded DNA phages using two model Escherichia coli strains (K-12 and BL21) with known sequence divergence to demonstrate strain-specific differences. However, to date, efforts to rapidly and comprehensively identify bacterial host factors important in phage infection and resistance have yet to be fully realized. Lindsay Adler Rapidshare Library Drivers Of Microbial.
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