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Yet, ECR strains of\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      carrying diverse amino acid changes in Fks1 and Fks2 are increasingly reported as breakthrough infections. Nonetheless, the impact of equivalent mutations in different\n                      <jats:italic toggle=\"yes\">FKS<\/jats:italic>\n                      alleles on fitness has not been systematically studied. Herein, we employed a diverse array of\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      models to address these questions among clinically relevant ECR mutants. All ECR mutants retained fitness during interaction with THP1 macrophages and neutrophils. Whereas a strain with a Fks2\n                      <jats:sup>F659del<\/jats:sup>\n                      or\n                      <jats:italic toggle=\"yes\">fks2\u0394<\/jats:italic>\n                      showed fitness defects during interaction with macrophages and neutrophils. Fks2\n                      <jats:sup>F659del<\/jats:sup>\n                      showed a unique susceptibility to numerous stresses, especially the combination of alternative carbon sources, low pH, and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      . Consistent with failure in mounting adaptive oxidative stress response during exposure to H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      , transcriptomic analysis of intracellular Fks2\n                      <jats:sup>F659del<\/jats:sup>\n                      highlighted the dysregulation of oxidative stress response genes, whereas intracellular\n                      <jats:italic toggle=\"yes\">fks2\u0394<\/jats:italic>\n                      showed hallmarks of metabolic dysregulation. Intriguingly, the Fks2\n                      <jats:sup>F659del<\/jats:sup>\n                      mutant was outcompeted by wild type and Fks2\n                      <jats:sup>F659V<\/jats:sup>\n                      in\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      gut colonization and systemic infection models. Importantly, whereas both\n                      <jats:italic toggle=\"yes\">FKS1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                      were required to establish gut colonization, only\n                      <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                      was required for systemic infection. Therefore, our study supports the notion that the prevalence of ECR mutants among\n                      <jats:italic toggle=\"yes\">C. glabrata<\/jats:italic>\n                      strains is likely driven by its ability to retain fitness across diverse niches. Furthermore, we identified that the essentiality of\n                      <jats:italic toggle=\"yes\">FKS1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">FKS2<\/jats:italic>\n                      is similarly dictated by niche-specific requirements.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01801-25","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:01:26Z","timestamp":1774270886000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional assessment of in-host fitness costs of echinocandin resistance in the opportunistic fungal pathogen\n                    <i>Candida glabrata<\/i>\n                    reveals the niche-specific requirement for\n                    <i>FKS1<\/i>\n                    and\n                    <i>FKS2<\/i>\n                    during infection and gut colonization"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-4841","authenticated-orcid":true,"given":"Amir","family":"Arastehfar","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Massachusetts General Hospital","place":["Boston, USA"]},{"name":"Department of Medicine, Harvard Medical School","place":["Boston, USA"]},{"id":[{"id":"https:\/\/ror.org\/03pvr2g57","id-type":"ROR","asserted-by":"publisher"}],"name":"University Hospital Wuerzburg, Medical Hospital II","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnaz","family":"Daneshnia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Massachusetts General Hospital","place":["Boston, 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