Targeting the calcineurin pathway enhances ergosterol biosynthesis inhibitors against Trichophyton mentagrophytes in vitro and in a human skin infection model.
Fluconazole-FK506 or fluconazole-cyclosporine drug combinations were tested in an ex vivo Trichophyton mentagrophytes human skin infection model. Conidia colonization was monitored by scanning electron microscopy over a 7-day treatment period. The fluconazole-FK506 combination demonstrated the most obvious advantage over single-drug therapy by clearing conidia and protecting skin from damage at low drug concentrations.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Chiatogu
C
Onyewu
Emily
E
Eads
Wiley A
WA
Schell
John R
JR
Perfect
Yehuda
Y
Ullmann
Gil
G
Kaufman
Benjamin A
BA
Horwitz
Israela
I
Berdicevsky
Joseph
J
Heitman
D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D019703:Calcineurin / Q000502:physiology*; D015169:Colony Count, Microbial; D003470:Culture Media; D016572:Cyclosporine / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004875:Ergosterol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009281:Naphthalenes / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000382:microbiology / Q000473:pathology; D016559:Tacrolimus / Q000627:therapeutic use; D000077291:Terbinafine; D014005:Tinea / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D014249:Trichophyton / Q000187:drug effects / Q000378:metabolism*
D000935:Antifungal Agents; D003470:Culture Media; D007166:Immunosuppressive Agents; D009281:Naphthalenes; D016572:Cyclosporine; D015725:Fluconazole; D019703:Calcineurin; D000077291:Terbinafine; D016559:Tacrolimus; D004875:Ergosterol