{"doi":"10.1073/pnas.0505401102","title":"Negative regulation of\n                    <i>Salmonella</i>\n                    pathogenicity island 2 is required for contextual control of virulence during typhoid","abstract":"<jats:p>\n                    <jats:italic>Salmonella enterica</jats:italic>\n                    relies on a type III secretion system encoded in\n                    <jats:italic>Salmonella</jats:italic>\n                    pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at systemic sites during typhoid. SPI-2 virulence is induced upon entry into macrophages, but the mechanisms of SPI-2 gene control\n                    <jats:italic>in vivo</jats:italic>\n                    remain unclear, particularly with regard to negative regulators that control the contextual activation of SPI-2. Here, we identified and characterized YdgT as a negative modulator of the SPI-2 pathogenicity island and established that this negative regulation is central to systemic pathogenesis because\n                    <jats:italic>ydgT</jats:italic>\n                    mutants overexpressing typhoid virulence genes were ultimately attenuated during infection.\n                    <jats:italic>ydgT</jats:italic>\n                    mutants displayed a biphasic virulence phenotype during\n                    <jats:italic>in vivo</jats:italic>\n                    competitive infections that consisted of an early “gain-of-virulence” dependent on SPI-2 activation, followed by attenuation later in infection indicating that proper contextual regulation of SPI-2 by YdgT is necessary for full virulence during systemic colonization. These data suggest that overexpression of virulence-associated type III secretion genes can have an adverse effect on bacterial pathogenesis\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2005,"id":622235,"datarank":0.6937459219926407,"base_score":4.624972813284271,"endowment":4.624972813284271,"self_citation_contribution":0.6937459219926407,"citation_network_contribution":0.0,"self_endowment_contribution":0.6937459219926407,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":101,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":125998,"name":"Mark E. Wickham","orcid":null,"position":1,"is_corresponding":false},{"id":1607596,"name":"Michael J. Lowden","orcid":null,"position":2,"is_corresponding":false},{"id":125999,"name":"Nat F. Brown","orcid":null,"position":3,"is_corresponding":false},{"id":126002,"name":"B. Brett Finlay","orcid":null,"position":4,"is_corresponding":false},{"id":1174825,"name":"Brian K. Coombes","orcid":"0000-0001-9883-1010","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Negative regulation of\n                    <i>Salmonella</i>\n                    pathogenicity island 2 is required for contextual control of virulence during typhoid","abstract":"<jats:p>\n                    <jats:italic>Salmonella enterica</jats:italic>\n                    relies on a type III secretion system encoded in\n                    <jats:italic>Salmonella</jats:italic>\n                    pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at systemic sites during typhoid. SPI-2 virulence is induced upon entry into macrophages, but the mechanisms of SPI-2 gene control\n                    <jats:italic>in vivo</jats:italic>\n                    remain unclear, particularly with regard to negative regulators that control the contextual activation of SPI-2. Here, we identified and characterized YdgT as a negative modulator of the SPI-2 pathogenicity island and established that this negative regulation is central to systemic pathogenesis because\n                    <jats:italic>ydgT</jats:italic>\n                    mutants overexpressing typhoid virulence genes were ultimately attenuated during infection.\n                    <jats:italic>ydgT</jats:italic>\n                    mutants displayed a biphasic virulence phenotype during\n                    <jats:italic>in vivo</jats:italic>\n                    competitive infections that consisted of an early “gain-of-virulence” dependent on SPI-2 activation, followed by attenuation later in infection indicating that proper contextual regulation of SPI-2 by YdgT is necessary for full virulence during systemic colonization. These data suggest that overexpression of virulence-associated type III secretion genes can have an adverse effect on bacterial pathogenesis\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>","is_dataset_classified":null,"base_score":4.624972813284271,"endowment":4.624972813284271,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16301528","pmcid":"PMC1297660","openalex_id":"https://openalex.org/W2115778087","authors":[],"funders":[],"total_grants":0,"fwci":8.2725,"citation_percentile":0.97369986,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":8},{"year":2014,"count":9},{"year":2015,"count":3},{"year":2016,"count":5},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2021,"count":1},{"year":2022,"count":3},{"year":2023,"count":3},{"year":2024,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1297660","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1297660","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0505401102","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0505401102","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16301528","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC1297660","host_type":"repository"}],"fields_of_study":["Salmonella and Campylobacter epidemiology","Vibrio bacteria research studies","Escherichia coli research studies","Animals","Bacterial Proteins","Cell Line","DNA-Binding Proteins","Gene Expression Profiling","Gene Expression Regulation, Bacterial","HeLa Cells","Humans","Membrane Proteins","Mice","Reverse Transcriptase Polymerase Chain Reaction","Salmonella typhi","Typhoid Fever","Virulence"],"mesh_terms":["Animals","Bacterial Proteins","Cell Line","DNA-Binding Proteins","HeLa Cells","Humans","Membrane Proteins","Salmonella typhi","Typhoid Fever","Virulence","Gene Expression Regulation, Bacterial","Reverse Transcriptase Polymerase Chain Reaction","Gene Expression Profiling","Mice","Hela Cells"],"keywords":["Virulence","Pathogenicity island","Biology","Salmonella enterica","Salmonella","Microbiology","Secretion","Typhoid fever","Mutant","Type three secretion system","Phenotype","Gene","Virology","Genetics","Bacteria"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T18:46:47.928247Z","pmid":null,"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":[]}