{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336487/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Salmonella enterica subsp. enterica serovar Typhi"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336487"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Native Pathogen-Phage Networks Reveal Multilayered Defense and Gut-Active Antiphage Immunity II","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":"GSE336487","cross_references":{"GSM":["GSM9836181","GSM9836170","GSM9836180","GSM9836174","GSM9836185","GSM9836163","GSM9836184","GSM9836173","GSM9836172","GSM9836183","GSM9836171","GSM9836182","GSM9836178","GSM9836167","GSM9836166","GSM9836177","GSM9836165","GSM9836176","GSM9836186","GSM9836175","GSM9836164","GSM9836169","GSM9836168","GSM9836179"],"GPL":["37144"],"GSE":["336487"],"taxon":["Salmonella enterica subsp. enterica serovar Typhi"]}}