{"doi":"10.1101/2020.07.24.218685","title":"Genes influencing phage host range in <i>Staphylococcus aureus</i> on a species-wide scale","abstract":"Staphylococcus aureus is a human pathogen that causes serious diseases ranging from skin infections to septic shock. Bacteriophages (\"phages\") are both natural killers of S. aureus , offering therapeutic possibilities, as well as important vectors of horizontal gene transfer in the species. Here, we used high-throughput approaches to understand the genetic basis of strain-to-strain variation in sensitivity to phages, which defines the host range. We screened 259 diverse S. aureus strains covering more than 40 sequence types for sensitivity to eight phages, which were representatives of the three phage classes that infect the species. The phages were variable in host range, each infecting between 73 and 257 strains. Using genome-wide association approaches, we identified putative loci that affect host range and validated their function using USA300 transposon knockouts. In addition to rediscovering known host range determinants, we found several previously unreported genes affecting bacterial growth during phage infection, including trpA , phoR , isdB , sodM , fmtC , and relA . We used the data from our host range matrix to develop predictive models that achieved between 40 and 95% accuracy. This work illustrates the complexity of the genetic basis for phage susceptibility in S. aureus but also shows that with more data, we may be able to understand much of the variation. With a knowledge of host range determination, we can rationally design phage therapy cocktails that target the broadest host range of S. aureus strains and address basic questions regarding phage-host interactions, such as the impact of phage on S. aureus evolution.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125208,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"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":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571864,"name":"Kyle Winston","orcid":null,"position":1,"is_corresponding":false},{"id":570986,"name":"Shiyu Ji","orcid":"0009-0005-5245-1115","position":2,"is_corresponding":false},{"id":570987,"name":"Junting Wang","orcid":"0000-0003-3041-4944","position":3,"is_corresponding":false},{"id":571865,"name":"Michelle N. Hargita Davis","orcid":null,"position":4,"is_corresponding":false},{"id":570988,"name":"Claudia Solís‐Lemus","orcid":"0000-0002-9789-8915","position":5,"is_corresponding":false},{"id":311517,"name":"Timothy D. Read","orcid":"0000-0001-8966-9680","position":6,"is_corresponding":false},{"id":570985,"name":"Abraham Moller","orcid":"0000-0002-7324-8678","position":0,"is_corresponding":true}],"reference_count":114,"raw_metadata":null,"created_at":"2026-07-18T23:15:15.482227Z","pmid":null,"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":[]}