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Evasion of host defenses relies on a protective polysaccharide capsule, regulated, in part, by the GATA-like transcription factor Gat201. Gat201 additionally contributes to virulence through capsule-independent mechanisms. Here, we show that Gat201 affects the proliferation of\n                      <jats:italic toggle=\"yes\">C. neoformans<\/jats:italic>\n                      : in RPMI-1640 cell culture media at an alkaline pH that restricts wild-type cell growth,\n                      <jats:italic toggle=\"yes\">gat201<\/jats:italic>\n                      \u2206 strains show increased budding, growth, and viability. RNA-seq analysis shows that Gat201 pathway genes, including co-factors\n                      <jats:italic toggle=\"yes\">GAT204<\/jats:italic>\n                      and LIV3, are rapidly activated within minutes of inoculating\n                      <jats:italic toggle=\"yes\">C. neoformans<\/jats:italic>\n                      in RPMI media, and strains mutated for\n                      <jats:italic toggle=\"yes\">GAT204<\/jats:italic>\n                      and, to a lesser extent,\n                      <jats:italic toggle=\"yes\">LIV3<\/jats:italic>\n                      also show improved growth. The effect of Gat201 on growth is pH-dependent:\n                      <jats:italic toggle=\"yes\">gat201<\/jats:italic>\n                      \u2206 cells grow better than wild-type cells at high pH but worse than wild-type cells at neutral pH, in otherwise identical media. Together, this identifies the Gat201 pathway as an alkaline-responsive regulator of proliferation: Gat201 appears to govern an environment-dependent trade-off between proliferation and production of the defensive capsule. Furthermore, evolutionary analysis shows that Gat201 is in a subfamily of GATA-like transcription factors that is conserved within diverse fungi but absent in model yeasts. Together, our findings urge improved understanding of proliferation in diverse environmental niches in order to understand the mechanistic basis of fungal pathogenesis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Infectious microorganisms must adapt to differences between external and host environments in order to colonize and cause disease.\n                        <jats:italic toggle=\"yes\">Cryptococcus neoformans<\/jats:italic>\n                        is an encapsulated fungal pathogen that can infect human airways and travel to the brain to cause life-threatening meningitis. The airway is a dynamic environment characterized by nutrient limitation, high temperature (37\u00b0C), CO\n                        <jats:sub>2<\/jats:sub>\n                        , and transiently high pH (&gt;8.5). In both the lung and brain, fungal proliferation through budding is a major driver of pathogenesis; however, the regulators of\n                        <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                        proliferation are poorly understood and distinct from other model yeasts. In this work, we explore how\n                        <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                        adapts to shifting environments and identify that the transcription factor Gat201, known to regulate capsule production, negatively regulates proliferation under alkaline conditions. Our findings highlight the need for improved understanding of proliferation\/adaptation and its regulation in non-model systems.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00191-25","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T09:00:13Z","timestamp":1749027613000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["The GATA-like transcription factor Gat201 determines alkaline-restricted growth in\n                    <i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-9062","authenticated-orcid":false,"given":"Elizabeth S.","family":"Hughes","sequence":"first","affiliation":[{"name":"Institute for Cell Biology, and Centre for Engineering Biology, School of Biological Sciences, The University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8708-2480","authenticated-orcid":false,"given":"Laura R.","family":"Tuck","sequence":"additional","affiliation":[{"name":"Institute for Cell Biology, and Centre for Engineering Biology, School of Biological Sciences, The University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6521-4362","authenticated-orcid":false,"given":"Zhenzhen","family":"He","sequence":"additional","affiliation":[{"name":"Institute for Cell Biology, and Centre for Engineering Biology, School of Biological Sciences, The University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8051-2302","authenticated-orcid":true,"given":"Elizabeth R.","family":"Ballou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vbzva31","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Centre for Medical Mycology, The University of Exeter","place":["Exeter, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8025-6361","authenticated-orcid":true,"given":"Edward W. 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