{"doi":"10.1101/2024.02.06.579193","title":"<i>De novo</i> mutations mediate phenotypic switching in an opportunistic human lung pathogen","abstract":"Abstract Bacteria evolving within human hosts encounter selective tradeoffs that render mutations adaptive in one context and deleterious in another. Here, we report that the cystic fibrosis-associated pathogen Burkholderia dolosa overcomes in-human selective tradeoffs by acquiring successive point mutations that alternate phenotypes. We sequenced the whole genomes of 931 respiratory isolates from two recently infected patients and an epidemiologically-linked, chronically-infected patient. These isolates are contextualized using 112 historical genomes from the same outbreak strain. Within both newly infected patients, diverse parallel mutations that disrupt O-antigen expression quickly arose, comprising 29% and 63% of their B. dolosa communities by 3 years. The selection for loss of O-antigen starkly contrasts with our previous observation of parallel O-antigen-restoring mutations after many years of chronic infection in the historical outbreak. Experimental characterization revealed that O-antigen loss increases uptake in immune cells while decreasing competitiveness in the mouse lung. We propose that the balance of these pressures, and thus whether O-antigen expression is advantageous, depends on tissue localization and infection duration. These results suggest that mutation-driven alternation during infection may be more frequent than appreciated and is underestimated without dense temporal sampling.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486651,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"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":581142,"name":"Matthew M. Schaefers","orcid":"0000-0001-7454-4180","position":1,"is_corresponding":false},{"id":865074,"name":"Christina Merakou","orcid":"0000-0002-2098-599X","position":2,"is_corresponding":false},{"id":1174013,"name":"K. Mansour","orcid":"0009-0006-1498-441X","position":3,"is_corresponding":false},{"id":1330838,"name":"Georgia Lagoudas","orcid":null,"position":4,"is_corresponding":false},{"id":445387,"name":"Ashley R. Cross","orcid":"0000-0003-3858-3902","position":5,"is_corresponding":false},{"id":311518,"name":"Joanna B. Goldberg","orcid":"0000-0002-5285-5188","position":6,"is_corresponding":false},{"id":73904,"name":"Roy Kishony","orcid":"0000-0002-5013-5072","position":7,"is_corresponding":false},{"id":336827,"name":"Ahmet Uluer","orcid":"0000-0003-2335-4242","position":8,"is_corresponding":false},{"id":276829,"name":"Alexander J. McAdam","orcid":"0009-0005-6922-4760","position":9,"is_corresponding":false},{"id":89096,"name":"Paul C. Blainey","orcid":"0000-0002-4889-8783","position":10,"is_corresponding":false},{"id":671912,"name":"Sara O. Vargas","orcid":"0000-0002-7743-6422","position":11,"is_corresponding":false},{"id":1327627,"name":"Tami D. Lieberman","orcid":"0000-0003-1681-2313","position":12,"is_corresponding":false},{"id":424744,"name":"Gregory P. Priebe","orcid":"0000-0001-9831-0354","position":13,"is_corresponding":false},{"id":806440,"name":"Alexandra J. Poret","orcid":"0000-0002-0723-987X","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"38370793","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":[]}