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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,6,17]]},"abstract":"<jats:p>\n                    Fungal pathogens infect billions and kill millions of people each year. Many of these pathogens have evolved strategies to evade our antifungal immune defenses.\n                    <jats:italic toggle=\"yes\">Candida albicans,<\/jats:italic>\n                    for example, masks the proinflammatory pathogen-associated molecular pattern (PAMP) \u03b2-1,3-glucan, in response to specific host signals such as lactate. In\n                    <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                    , most \u03b2-1,3-glucan lies in the inner cell wall shielded, by the outer mannan layer, from recognition by certain immune cells such as macrophages. \u03b2-1,3-glucan that becomes exposed at the cell surface can be shaved off by secreted enzymes. By integrating mathematical modeling with experimentation, we show that the dynamics of this shaving, together with the dynamics of \u03b2-1,3-glucan exposure during growth, can account for a range of \u03b2-1,3-glucan masking phenotypes. The mathematical model accurately simulates the dynamics of \u03b2-1,3-glucan exposure during growth and predicts levels of \u03b2-1,3-glucan shaving under a variety of conditions, revealing how subtle differences in growth contribute to observed variabilities in lactate-induced \u03b2-1,3-glucan masking. For example, clinical isolates previously thought to display minimal lactate-induced masking are shown to mask robustly. Using a range of\n                    <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                    mutants, we confirm the importance of Gpr1\/Gpa2-protein kinase A signaling for lactate-induced \u03b2-1,3-glucan shaving and define the contributions of the Xog1 and Eng1 glucanases to this shaving. Furthermore, examination of a shielding-defective\n                    <jats:italic toggle=\"yes\">C. albicans mnn2<\/jats:italic>\n                    x6 mutant confirms that both \u03b2-1,3-glucan shaving and shielding contribute to the dynamism of \u03b2-1,3-glucan masking at the fungal cell surface. Dynamism in PAMP masking is likely to be relevant to other fungal pathogens of humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2423864122","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T15:00:42Z","timestamp":1749481242000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["Protein kinase A signaling regulates immune evasion by shaving and concealing fungal \u03b2-1,3-glucan"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4328-3912","authenticated-orcid":false,"given":"Arnab","family":"Pradhan","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0055-2211","authenticated-orcid":false,"given":"Olga A.","family":"Nev","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Leaves","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg A.","family":"Nev","sequence":"additional","affiliation":[{"name":"Software Consultant","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxi","family":"Ma","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Milne","sequence":"additional","affiliation":[{"name":"Microscopy and Histology Facility, Institute of Medical Sciences, University of Aberdeen","place":["Aberdeen, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1900-0308","authenticated-orcid":false,"given":"Grace","family":"Patterson","sequence":"additional","affiliation":[{"name":"Bioimaging Centre, Department of Biosciences, University of Exeter","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center","place":["Nijmegen, The Netherlands"]},{"name":"Department for Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars P.","family":"Erwig","sequence":"additional","affiliation":[{"name":"Cancer Research UK","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8456-7458","authenticated-orcid":false,"given":"Rhys A.","family":"Farrer","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon D.","family":"Brown","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, Department of Biosciences, Faculty of Health and Life Sciences","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-6227","authenticated-orcid":false,"given":"Hugo A.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Mathematics Institute, University of Warwick","place":["Coventry, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2776-5850","authenticated-orcid":false,"given":"Neil A. 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