{"doi":"10.1101/2024.05.21.595064","title":"Inducible transposon mutagenesis for genome-scale forward genetics","abstract":"Transposon insertion sequencing (Tn-seq) is a powerful method for genome-scale functional genetics in bacteria. However, its effectiveness is often limited by a lack of mutant diversity, caused by either inefficient transposon delivery or stochastic loss of mutants due to population bottlenecks. Here, we introduce \"InducTn-seq\", which leverages inducible mutagenesis for temporal control of transposition. InducTn-seq generates millions of transposon mutants from a single colony, enabling the sensitive detection of subtle fitness defects and transforming binary classifications of gene essentiality into a quantitative fitness measurement across both essential and non-essential genes. Using a mouse model of infectious colitis, we show that InducTn-seq bypasses a highly restrictive host bottleneck to generate a diverse transposon mutant population from the few cells that initiate infection, revealing the role of oxygen-related metabolic plasticity in pathogenesis. Overall, InducTn-seq overcomes the limitations of traditional Tn-seq, unlocking new possibilities for genome-scale forward genetic screens in bacteria.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490986,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"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":991015,"name":"Ian W. Campbell","orcid":"0000-0003-3019-2560","position":1,"is_corresponding":false},{"id":908877,"name":"Emily Sullivan","orcid":"0000-0001-9558-3883","position":2,"is_corresponding":false},{"id":1327557,"name":"Julia A. Hotinger","orcid":"0000-0003-2427-5482","position":3,"is_corresponding":false},{"id":657520,"name":"Karthik Hullahalli","orcid":"0000-0003-3064-2090","position":4,"is_corresponding":false},{"id":332461,"name":"Matthew K. Waldor","orcid":"0000-0003-1843-7000","position":5,"is_corresponding":false},{"id":352845,"name":"David W. Basta","orcid":"0000-0003-4176-6566","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T02:08:41.211111Z","pmid":"38826325","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":[]}