{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:52:53Z","timestamp":1790175173980,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"ECOSNord\/COLCIENCIAS","award":["C17S01"],"award-info":[{"award-number":["C17S01"]}]},{"name":"Pontificia Universidad Javeriana in Bogot\u00e1, Colombia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In recent decades, Candida glabrata has emerged as a frequent cause of life-threatening fungal infection. In C. glabrata, echinocandin resistance is associated with mutations in FKS1\/FKS2 (\u03b2-1,3-glucan synthase). The calmodulin\/calcineurin pathway is implicated in response to antifungal stress and calcineurin gene disruption specifically reverses Fks2-mediated resistance of clinical isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We evaluated the impact of calmodulin inhibition by fluphenazine in two caspofungin-resistant C. glabrata isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C. glabrata isolates were identified by ITS1\/ITS4 (where ITS stands for internal transcribed spacer) sequencing and the echinocandin target FKS1\/FKS2 genes were sequenced. Susceptibility testing of caspofungin in the presence of fluphenazine was performed by a modified CLSI microbroth dilution method. The effect of the fluphenazine\/caspofungin combination on heat stress (37\u00b0C or 40\u00b0C), oxidative stress (0.2 and 0.4\u2009mM menadione) and biofilm formation (polyurethane catheter) was analysed. A Galleria mellonella model using blastospores (1\u205f\u00d7\u205f109\u2009cfu\/mL) was developed to evaluate the impact of this combination on larval survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>F659del was found in the FKS2 gene of both resistant strains. In these clinical isolates, fluphenazine increased susceptibility to caspofungin and reduced their thermotolerance. Furthermore, the fluphenazine\/caspofungin combination significantly impaired biofilm formation in an in vitro polyurethane catheter model. All these features participated in the increasing survival of infected G. mellonella after combination treatment in comparison with caspofungin alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In a repurposing strategy, our findings confirm that calmodulin could provide a relevant target in life-threatening fungal infectious diseases.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkz565","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T12:37:17Z","timestamp":1579610237000},"page":"1187-1193","source":"Crossref","is-referenced-by-count":15,"title":["Impact of calmodulin inhibition by fluphenazine on susceptibility, biofilm formation and pathogenicity of caspofungin-resistant Candida glabrata"],"prefix":"10.1093","volume":"75","author":[{"given":"Andr\u00e9s","family":"Ceballos Garzon","sequence":"first","affiliation":[{"name":"Unidad de Prote\u00f3mica y Micosis Humanas, Grupo de Enfermedades Infecciosas Departamento de Microbiolog\u00eda, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogot\u00e1 D.C., Colombia"},{"name":"Department of Parasitology and Medical Mycology, University of Nantes, Nantes Atlantique Universities, Faculty of Pharmacy, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Amado","sequence":"first","affiliation":[{"name":"Unidad de Prote\u00f3mica y Micosis Humanas, Grupo de Enfermedades Infecciosas Departamento de Microbiolog\u00eda, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogot\u00e1 D.C., Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Robert","sequence":"first","affiliation":[{"name":"Department of Parasitology and Medical Mycology, University of Nantes, Nantes Atlantique Universities, Faculty of Pharmacy, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M","family":"Parra 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