{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336350/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Salmonella enterica subsp. enterica serovar Typhimurium str. D23580"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336350"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Native Pathogen-Phage Networks Reveal Multilayered Defense and Gut-Active Antiphage Immunity","description":"Bacteriophages strongly shape pathogen evolution, yet the determinants of phage susceptibility in native bacterial backgrounds, and their consequences within mammalian hosts, remain poorly defined. Here, we mapped >1,000 interactions between 20 diverse Salmonella isolates and 52 wild phages from global disease reservoirs, integrating genome-scale fitness profiling with comparative genomics. Receptor identity and surface phase variation, including Hin-mediated flagellar switching, explained ~67% of phage susceptibility patterns, identifying cell-surface architecture as the major determinant of phage host range in Salmonella. Among resistance phenotypes not explained by surface features, we discovered AppA, a prophage-encoded defense factor that abrogates phage replication within its native host. AppA inhibits phage DNA packaging through functional mimicry of a terminase assembly interface, revealing a previously unrecognized mechanism of phage defense. AppA is expressed under conditions encountered during mammalian infection and suppresses phage expansion in the murine gut, demonstrating that prophage-encoded single-gene defenses can shape infection outcomes in vivo.","dates":{"publication":"2026/08/31"},"accession":"GSE336350","cross_references":{"GSM":["GSM9833163","GSM9833164","GSM9833161","GSM9833162","GSM9833167","GSM9833200","GSM9833201","GSM9833168","GSM9833165","GSM9833166","GSM9833204","GSM9833205","GSM9833169","GSM9833202","GSM9833203","GSM9833208","GSM9833209","GSM9833206","GSM9833207","GSM9833170","GSM9833171","GSM9833174","GSM9833175","GSM9833172","GSM9833173","GSM9833178","GSM9833211","GSM9833212","GSM9833179","GSM9833176","GSM9833210","GSM9833177","GSM9833215","GSM9833216","GSM9833213","GSM9833214","GSM9833219","GSM9833217","GSM9833218","GSM9833181","GSM9833182","GSM9833180","GSM9833185","GSM9833186","GSM9833183","GSM9833184","GSM9833189","GSM9833222","GSM9833187","GSM9833220","GSM9833188","GSM9833221","GSM9833192","GSM9833193","GSM9833190","GSM9833191","GSM9833196","GSM9833197","GSM9833194","GSM9833195","GSM9833198","GSM9833199"],"GPL":["37136"],"GSE":["336350"],"taxon":["Salmonella enterica subsp. enterica serovar Typhimurium str. D23580"]}}