{"doi":"10.1101/2024.04.20.590424","title":"Systematic genome-wide discovery of host factors governing bacteriophage infectivity","abstract":"Bacterial host factors regulate the infection cycle of bacteriophages. Except for some well-studied host factors (e.g., receptors or restriction-modification systems), the contribution of the rest of the host genome on phage infection remains poorly understood. We developed PHAGEPACK, a pooled assay that systematically and comprehensively measures each host-gene impact on phage fitness. PHAGEPACK combines CRISPR interference with phage packaging to link host perturbation to phage fitness during active infection. Using PHAGEPACK, we constructed a genome-wide map of genes impacting T7 phage fitness in permissive E. coli, revealing pathways previously unknown to affect phage packaging. When applied to the non-permissive E. coli O121, PHAGEPACK identified pathways leading to host resistance; their removal increased phage susceptibility up to a billion-fold. Bioinformatic analysis indicates phage genomes carry homologs or truncations of key host factors, potentially for fitness advantage. In summary, PHAGEPACK offers valuable insights into phage-host interactions, phage evolution, and bacterial resistance.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488377,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":711659,"name":"Cody Martin","orcid":"0000-0001-7610-9537","position":1,"is_corresponding":false},{"id":583220,"name":"Phil Huss","orcid":"0000-0003-4064-9333","position":2,"is_corresponding":false},{"id":259592,"name":"Jason M. Peters","orcid":"0000-0003-2722-8382","position":3,"is_corresponding":false},{"id":40438,"name":"Karthik Anantharaman","orcid":"0000-0002-9584-2491","position":4,"is_corresponding":false},{"id":991226,"name":"Srivatsan Raman","orcid":"0000-0002-5673-6944","position":5,"is_corresponding":false},{"id":1332759,"name":"Chutikarn Chitboonthavisuk","orcid":"0000-0002-9496-6046","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:15.008850Z","pmid":"38659955","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}