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The transmissibility and intrinsic antibiotic resistance of\n              <jats:italic>B. cenocepacia<\/jats:italic>\n              pose a significant challenge in healthcare settings. In this study, with the aim to identify novel drug targets to fight\n              <jats:italic>B. cenocepacia<\/jats:italic>\n              infections, we employed a genome-wide transposon sequencing (Tn-seq) approach to unravel fitness determinants required for survival in\n              <jats:italic>Galleria mellonella<\/jats:italic>\n              (\n              <jats:italic>in vivo<\/jats:italic>\n              infection model) and pig lung tissue (\n              <jats:italic>ex vivo<\/jats:italic>\n              organ model). A total of 698 and 117 fitness genes were identified for each of the models, respectively, and 62 genes were found to be important for both. To confirm our results, we constructed individual mutants in selected genes and validated their fitness in the two models. Among the various determinants identified was a rare genomic island (\n              <jats:italic>I35_RS03700\u2013I35_RS03770<\/jats:italic>\n              ) involved in O-antigen and lipopolysaccharide synthesis. We demonstrate that this gene cluster is required for virulence in the\n              <jats:italic>G. mellonella<\/jats:italic>\n              infection model but, by contrast, counteracts efficient colonization of pig lung tissue. Our results highlight the power of the Tn-seq approach to unravel fitness determinants that could be used as therapeutic targets in the future and show that the choice of the infection model for mutant selection is paramount.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The opportunistic pathogen\n              <jats:italic>Burkholderia cenocepacia<\/jats:italic>\n              has been associated with nosocomial infections in healthcare facilities, where it can cause outbreaks involving infections of the bloodstream, respiratory tract, and urinary tract as well as severe complications in immunocompromised patients. With the aim to identify novel targets to fight\n              <jats:italic>B. cenocepacia<\/jats:italic>\n              infections, we have used a genome-wide approach to unravel fitness genes required for host colonization in a clinical strain,\n              <jats:italic>B. cenocepacia<\/jats:italic>\n              H111. Among the various determinants that we identified is a rare genomic island that modifies the bacterial lipopolysaccharide. Our results highlight the power of the transposon sequencing approach to identify new targets for infection treatment and show the importance of using different infection models.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msystems.01354-24","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T13:00:26Z","timestamp":1742389226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Unraveling\n            <i>Burkholderia cenocepacia<\/i>\n            H111 fitness determinants using two animal models"],"prefix":"10.1128","volume":"10","author":[{"given":"Sarah","family":"Paszti","sequence":"first","affiliation":[{"name":"Department of Plant and Microbial Biology, University of Zurich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gualdi","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of Zurich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-9123","authenticated-orcid":true,"given":"Marta","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of Zurich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Augusto","sequence":"additional","affiliation":[{"name":"Institute for Integrative Biology of the Cell (I2BC), University Paris-Saclay, CEA, CNRS","place":["Gif-sur-Yvette, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8449-5095","authenticated-orcid":true,"given":"Freya","family":"Harrison","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gibbet Hill Campus, University of Warwick","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7241-0864","authenticated-orcid":true,"given":"Leo","family":"Eberl","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of Zurich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10123-020-00151-z"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8221.1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/ijs.0.001123-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00248-011-9929-1"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1085"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2010.02343.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mjafi.2016.03.003"},{"key":"e_1_3_4_9_2","first-page":"551","article-title":"Outbreak of catheter-related Burkholderia cepacia sepsis acquired from contaminated ultrasonography gel: the importance of strengthening hospital infection control measures in low resourced settings","volume":"28","author":"Viderman D","year":"2020","unstructured":"Viderman D, Khudaibergenova M, Kemaikin V, Zhumadilov A, Poddighe D. 2020. 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