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Antimicrobial Agents and Chemotherapy, October 2007, p. 3743-3746, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00492-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Targeting the Calcineurin Pathway Enhances Ergosterol Biosynthesis Inhibitors against Trichophyton mentagrophytes In Vitro and in a Human Skin Infection Model{triangledown}

Chiatogu Onyewu,3 Emily Eads,2 Wiley A. Schell,2 John R. Perfect,2 Yehuda Ullmann,4 Gil Kaufman,5 Benjamin A. Horwitz,6 Israela Berdicevsky,5* and Joseph Heitman1,2,3*

Departments of Molecular Genetics and Microbiology,1 Medicine,2 Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710,3 Department of Plastic Surgery, Rambam Medical Center, Haifa, Israel,4 Faculty of Medicine, Molecular Microbiology,5 Biology, Technion—Israel Institute of Technology, Haifa, Israel6

Received 11 April 2007/ Returned for modification 24 May 2007/ Accepted 20 July 2007

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.

* Corresponding author. Mailing address for Joseph Heitman: Department of Molecular Genetics and Microbiology, 322 Carl Building, Box 3546, Research Drive, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu. Mailing address for Israela Berdicevsky: Department of Molecular Microbiology, Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 31096, Israel. Phone: (972) 48295293. Fax: (972) 48295225. E-mail: israelab{at}tx.technion.ac.il

{triangledown} Published ahead of print on 30 July 2007.

Antimicrobial Agents and Chemotherapy, October 2007, p. 3743-3746, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00492-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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