Calcineurin promotes infection of the cornea by Candida albicans and can be targeted to enhance fluconazole therapy.
In an established Candida albicans murine keratitis model, combination therapy with ophthalmic preparations of fluconazole and cyclosporine A (CsA) demonstrated in vivo drug synergy and effectively resolved wild-type C. albicans infection more rapidly than monotherapy with either drug. Calcineurin, the target of CsA, was also found to contribute to pathogenicity.
Onyewu
Chiatogu
C
Department of Ophthalmology, Wadsworth Bldg., Box 3802, Erwin Road, Duke University Eye Center, Durham, NC 27710, USA. afsha003@mc.duke.edu
Afshari
Natalie A
NA
Heitman
Joseph
J
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019703:Calcineurin / Q000502:physiology*; D065095:Calcineurin Inhibitors; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology*; D003316:Corneal Diseases / Q000188:drug therapy* / Q000382:microbiology*; D016572:Cyclosporine / Q000627:therapeutic use; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007634:Keratitis / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C
D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015725:Fluconazole; D019703:Calcineurin