{"doi":"10.26508/lsa.202503292","title":"PTEN modulates urinary tract infection susceptibility and shapes urothelial antibacterial defenses","abstract":"Despite advancements in our understanding of urinary tract infection (UTI) pathogenesis, UTIs remain a leading cause of morbidity, partly because of an incomplete understanding of the molecular pathways governing bladder antibacterial defenses. Here, we demonstrate that phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling, is a critical modulator of bladder urothelial immune defenses and vulnerability to UTIs caused by uropathogenic Escherichia coli (UPEC). PTEN silencing in human bladder urothelial cells increases susceptibility to UPEC in vitro, and urothelial-specific PTEN knockout mice exhibit increased bacterial titers in the urine, bladder, and kidneys after in vivo transurethral UPEC infection. Mechanistically, PTEN deficiency enhances Akt phosphorylation, amplifying NFκB and FAK activity. Silencing NFκB or FAK in PTEN-deficient cells restores resistance to UPEC. These findings establish PTEN as an important regulator of bladder urothelial defenses, balancing immune activation and urothelial structural integrity to protect against UTI.","journal":"Life Science Alliance","year":2025,"id":570819,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":931717,"name":"Matthew S. Bochter","orcid":"0000-0001-9607-3770","position":1,"is_corresponding":false},{"id":451759,"name":"Sarah C. Linn","orcid":"0000-0003-4337-2966","position":2,"is_corresponding":false},{"id":1227965,"name":"Kristin Salamon","orcid":null,"position":3,"is_corresponding":false},{"id":428881,"name":"Brian Becknell","orcid":"0000-0002-2750-4415","position":4,"is_corresponding":false},{"id":1114190,"name":"Hanna H. Cortado","orcid":null,"position":5,"is_corresponding":false},{"id":428876,"name":"Ashley R. Jackson","orcid":"0000-0002-1571-3906","position":6,"is_corresponding":false},{"id":699563,"name":"Laura Schwartz","orcid":"0000-0002-4056-3030","position":7,"is_corresponding":false},{"id":699566,"name":"John David Spencer","orcid":"0000-0001-5509-7135","position":8,"is_corresponding":false},{"id":722913,"name":"Aaron Simoni","orcid":"0000-0002-0657-3737","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40701780","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":[]}