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Understanding the mechanisms driving\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      adaptation during colonization of the airways of CF patients is of critical clinical importance. Previous studies by our group and others have shown that elevated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      , a characteristic feature of CF airways, positively regulates virulence factor production in\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      and triggers its transition to a biofilm mode of growth. To generate further insights into Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -dependent adaptations in this pathogen, we aimed to elucidate the regulatory impact of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      on its metabolism. To characterize Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -induced metabolic alterations, a global untargeted gas chromatography-mass spectrometry-based metabolomics study was performed for both intracellular and extracellular fractions of mid-log and stationary-phase\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      cultures. The altered metabolites were mapped to specific pathways, and selected transcriptional changes and phenotypic outcomes were assayed. Our findings showed that Ca\n                      <jats:sup>2+<\/jats:sup>\n                      regulates pathways involved in central carbon metabolism, nucleotide synthesis, the shikimate pathway, and glycogen metabolism in both mid-log- and stationary-phase cells. Furthermore, pathways involved in sequestering iron were induced by Ca\n                      <jats:sup>2+<\/jats:sup>\n                      during both growth phases. Overall, these results indicate that exposure to elevated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      , as within the CF airways, leads to metabolic adjustments and supports\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      survival in this environment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Individuals with the genetic disorder, cystic fibrosis (CF), are predisposed to developing chronic, life-threatening\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      ) infections. Elucidating the mechanisms that mediate the adaptation of\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      to the CF airways is essential for the development of new therapeutics to treat these infections. Previously, we have shown that elevated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      levels, such as those detected in CF airways, induce the production of multiple virulence factors, contributing to the overall pathogenicity of\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      . Here, we report that Ca\n                      <jats:sup>2+<\/jats:sup>\n                      regulates\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      metabolism, affecting multiple pathways, including central carbon, nucleotide, and shikimate pathways. These metabolic alterations contribute to significant physiological outcomes, some of which are pertinent to\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      virulence and survival within the host. These findings suggest that Ca\n                      <jats:sup>2+<\/jats:sup>\n                      can serve as a host factor that plays a significant role in\n                      <jats:italic toggle=\"yes\">Pa<\/jats:italic>\n                      patho-adaptation to CF airways.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aem.02419-25","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:01:42Z","timestamp":1781524902000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Calcium regulation of\n                    <i>Pseudomonas aeruginosa<\/i>\n                    metabolism"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7076-0755","authenticated-orcid":false,"given":"Mackenzie","family":"Hull","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ymr5447","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics, Oklahoma State University","place":["Stillwater, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"King","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ymr5447","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics, Oklahoma State University","place":["Stillwater, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Decker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ymr5447","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics, Oklahoma State University","place":["Stillwater, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-3867","authenticated-orcid":true,"given":"Marianna A.","family":"Patrauchan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ymr5447","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics, Oklahoma State University","place":["Stillwater, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12033"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2019.296"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00065"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11030664"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201404-166OC"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00477-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14631"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00005-09"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66194-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-13172-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11020063"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01138-07"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.15.5267-5277.2005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.4c00286"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.MBP-0003-2014"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-1800"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2012.02842.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2020.113369"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00269-18"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)39790-4"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1177\/000992286900800308"},{"key":"e_1_3_2_23_2","first-page":"114","article-title":"Composition of nasal secretion in patients with cystic fibrosis","volume":"88","author":"Lorin MI","year":"1976","unstructured":"Lorin MI, Gaerlan PF, Mandel ID, Denning CR. 1976. 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