Giuseppe
Emeritus
[Source: Antimicrobial Agents Chemotherapy, full text: (LINK). Abstract, edited.]
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In Vitro Activity of Calcineurin and Heat-Shock Protein 90 (Hsp90) Inhibitors Against Aspergillus fumigatus Azole- and Echinocandin-Resistant Strains
Fr?d?ric Lamoth 1, Praveen R. Juvvadi 1, Christopher Gehrke 1 and William J. Steinbach 1,2,*
Author Affiliations: <SUP>1</SUP>Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA; <SUP>2</SUP>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
ABSTRACT
Due to the limited number of antifungals and the emergence of resistance, new therapies against invasive aspergillosis are needed. We show that calcineurin inhibitors are active in vitro against both Aspergillus fumigatus azole- and echinocandin-resistant strains. The Hsp90 inhibitor geldanamycin had modest activity when used alone, but its combination with caspofungin or FK506 resulted in fungicidal activity against azole-resistant strains. Targeting the Hsp90-calcineurin axis is a promising alternative strategy against azole-resistant A. fumigatus strains.
FOOTNOTES
*Corresponding author: William J. Steinbach, Division of Pediatric Infectious Diseases, 427 Jones Building, Research Drive, Duke University Medical Center, Durham, NC 27710, Phone number: (919) 681-1504, Fax number: (919) 668-4859, E-mail: bill.steinbach@duke.edu
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
-Author Affiliations: <SUP>1</SUP>Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA; <SUP>2</SUP>Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA
ABSTRACT
Due to the limited number of antifungals and the emergence of resistance, new therapies against invasive aspergillosis are needed. We show that calcineurin inhibitors are active in vitro against both Aspergillus fumigatus azole- and echinocandin-resistant strains. The Hsp90 inhibitor geldanamycin had modest activity when used alone, but its combination with caspofungin or FK506 resulted in fungicidal activity against azole-resistant strains. Targeting the Hsp90-calcineurin axis is a promising alternative strategy against azole-resistant A. fumigatus strains.
FOOTNOTES
*Corresponding author: William J. Steinbach, Division of Pediatric Infectious Diseases, 427 Jones Building, Research Drive, Duke University Medical Center, Durham, NC 27710, Phone number: (919) 681-1504, Fax number: (919) 668-4859, E-mail: bill.steinbach@duke.edu
Copyright ? 2012, American Society for Microbiology. All Rights Reserved.
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