{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:56:54Z","timestamp":1787237814278,"version":"build-2736575974"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Gouvernement du Canada | Canadian Institutes of Health Research","award":["FDN-143202"],"award-info":[{"award-number":["FDN-143202"]}]},{"name":"German Research Foundation Priority Programme","award":["SPP 2225"],"award-info":[{"award-number":["SPP 2225"]}]},{"name":"Gouvernement du Canada | Canadian Institutes of Health Research","award":["FDN-154288"],"award-info":[{"award-number":["FDN-154288"]}]},{"name":"HHS | National Institutes of Health","award":["R01AI127375"],"award-info":[{"award-number":["R01AI127375"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2023,12,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    For the human fungal pathogen\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , metabolic flexibility and the ability to transition between yeast and filamentous growth states are key virulence traits that enable disease in the host. These traits are particularly important during the interaction of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    with macrophages, where the fungus must utilize multiple alternative carbon sources to survive after being phagocytosed, and filamentation is coupled to fungal escape and immune cell death. Here, we employed functional genomic screening of conditional-expression mutants covering &gt;50% of the\n                    <jats:italic>C. albicans<\/jats:italic>\n                    genome to identify genes selectively required for filamentation inside macrophages. Through manual and machine learning-based image analyses, we uncovered a role for the mitochondrial ribosome, respiration, and the SNF1 AMP-activated kinase complex in governing filamentous growth within the phagosome, suggesting that\n                    <jats:italic>C. albicans<\/jats:italic>\n                    relies on respiration to evade the antifungal activities of macrophages. We demonstrate that downregulating the expression of these genes reduces ATP levels and impedes filamentation as well as growth under monoculture conditions in medium lacking glucose. In co-culture with physiological glucose concentration, downregulation of genes involved in mitochondrial function and respiration prevented\n                    <jats:italic>C. albicans<\/jats:italic>\n                    from expanding within the phagosome, escaping, and inducing immune cell death. Together, our work provides new insights into the impact of metabolism on the interaction between\n                    <jats:italic>C. albicans<\/jats:italic>\n                    and macrophages, highlighting respiration and the SNF1 AMP-activated kinase as key effectors of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    metabolic flexibility and filamentation within phagocytes.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      is a leading human fungal pathogen that often causes life-threatening infections in immunocompromised individuals. The ability of\n                      <jats:italic>C. albicans<\/jats:italic>\n                      to transition between yeast and filamentous forms is key to its virulence, and this occurs in response to many host-relevant cues, including engulfment by host macrophages. While previous efforts identified\n                      <jats:italic>C. albicans<\/jats:italic>\n                      genes required for filamentation in other conditions, the genes important for this morphological transition upon internalization by macrophages remained largely enigmatic. Here, we employed a functional genomic approach to identify genes that enable\n                      <jats:italic>C. albicans<\/jats:italic>\n                      filamentation within macrophages and uncovered a role for the mitochondrial ribosome, respiration, and the SNF1 AMP-activated kinase complex. Additionally, we showed that glucose uptake and glycolysis by macrophages support\n                      <jats:italic>C. albicans<\/jats:italic>\n                      filamentation. This work provides insights into the metabolic dueling that occurs during the interaction of\n                      <jats:italic>C. albicans<\/jats:italic>\n                      with macrophages and identifies vulnerabilities in\n                      <jats:italic>C. albicans<\/jats:italic>\n                      that could serve as promising therapeutic targets.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02745-23","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T09:01:11Z","timestamp":1701421271000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Respiration supports intraphagosomal filamentation and escape of\n                    <i>Candida albicans<\/i>\n                    from macrophages"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7692-3424","authenticated-orcid":false,"given":"Nicola T.","family":"Case","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Westman","sequence":"additional","affiliation":[{"name":"Program in Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Hallett","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Plumb","sequence":"additional","affiliation":[{"name":"Program in Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiman","family":"Farheen","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Maxson","sequence":"additional","affiliation":[{"name":"Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie","family":"MacAlpine","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6218-2247","authenticated-orcid":true,"given":"Sean D.","family":"Liston","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6028-0425","authenticated-orcid":true,"given":"Bernhard","family":"Hube","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany"},{"name":"Institute of Microbiology, Friedrich Schiller University, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-0110","authenticated-orcid":false,"given":"Nicole","family":"Robbins","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Whitesell","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, 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