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The early immune response is critical in controlling\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      infection, but\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      has several strategies to evade host immune attack. Phagocytosis of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      blocks hyphal growth, limiting host damage and virulence, but how\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131\n                      <jats:italic toggle=\"yes\">C<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">albicans<\/jats:italic>\n                      mutants for altered virulence and phagocyte response. Infections with each of the seven hypovirulent mutants led to altered phagocyte recruitment and\/or phagocytosis, falling into four categories. Of particular interest among these is\n                      <jats:italic toggle=\"yes\">NMD5<\/jats:italic>\n                      , a predicted \u03b2-importin and newly identified virulence factor. The\n                      <jats:italic toggle=\"yes\">nmd5<\/jats:italic>\n                      \u2206\/\u2206 mutant fails to limit phagocytosis, and its virulence defects are eliminated when phagocyte activity is compromised, suggesting that its role in virulence is limited to immune evasion. These quantitative intravital imaging experiments are the first to document altered\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      \u2013phagocyte interactions for several additional mutants and clearly distinguish recruitment from phagocytic uptake, suggesting that\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      modulates both events. This initial large-scale screen of individual\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      mutants in a vertebrate, coupled with high-resolution imaging of\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      \u2013phagocyte interactions, provides a more nuanced view of how diverse mutations can lead to more effective phagocytosis, a key immune process that blocks germination and drives anti-fungal immunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      is part of the human microbial community and is a dangerous opportunistic pathogen, able to prevent its elimination by the host immune system. Although\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      avoids immune attack through several strategies, we still understand little about how it regulates when immune phagocytes get recruited to the infection site and when they engulf fungal cells. We tested over 130 selected\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      mutants for their ability to cause lethal infection and found several hypovirulent mutants, which provoked altered innate immune responses, resulting in lower overall inflammation and greater host survival. Of particular interest is\n                      <jats:italic toggle=\"yes\">NMD5<\/jats:italic>\n                      , which acts to limit fungal phagocytosis and is predicted to regulate the activity of stress-associated transcription factors. Our high-content screening was enabled by modeling\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      infection in transparent vertebrate zebrafish larva. Our findings help us understand how\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      survives immune attack during commensal and pathogenic growth, and may eventually inform new strategies for controlling disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00529-25","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T03:01:07Z","timestamp":1743735667000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Forward genetic screen in zebrafish identifies new fungal regulators that limit host-protective\n                    <i>Candida<\/i>\n                    -innate immune interaction"],"prefix":"10.1128","volume":"16","author":[{"given":"Bailey A.","family":"Blair","sequence":"first","affiliation":[{"name":"Department of Molecular & Biomedical Sciences, University of 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