Synergistic effects of geldanamycin with fluconazole are associated with reactive oxygen species in Candida tropicalis resistant to azoles and amphotericin B

References

• Nucci M, Colombo AL. Candidemia due to Candida tropicalis: clinical, epidemiologic, and microbiologic characteristics of 188 episodes occurring in tertiary care hospitals. Diagn Microbiol Infect Dis. 2007;58:77–82.
   PubMed Web of Science ®Google Scholar
• Kothavade RJ, Kura MM, Valand AG, et al. Candida tropicalis: its prevalence, pathogenicity and increasing resistance to fluconazole. J Med Microbiol. 2010;59:873–880.
   PubMed Web of Science ®Google Scholar
• Kohli A, Smriti N, Mukhopadhyay K, et al. In vitro low-level resistance to azoles in Candida albicans is associated with changes in membrane lipid fluidity and asymmetry. Antimicrob Agents Chemother. 2002;46:1046–1052.
   PubMed Web of Science ®Google Scholar
• White TC, Holleman S, Dy F, et al. Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob Agents Chemother. 2002;46:1704–1713.
   PubMed Web of Science ®Google Scholar
• Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39:309–317.
   PubMed Web of Science ®Google Scholar
• Mulu A, Kassu A, Anagaw B, et al. Frequent detection of “azole” resistant candida species among late presenting AIDS patients in northwest Ethiopia. BMC Infect Dis. 2013;13:82.
   PubMed Web of Science ®Google Scholar
• Kelly SL, Lamb DC, Kelly DE, et al. Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol delta5,6-desaturation. FEBS Lett. 1997;400:80–82.
   PubMed Web of Science ®Google Scholar
• Stebbins CE, Russo AA, Schneider C, et al. Crystal structure of an Hsp90–geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell. 1997;89:239–250.
   PubMed Web of Science ®Google Scholar
• Sreedhar AS, Mihály K, Pató B, et al. Hsp90 inhibition accelerates cell lysis. Anti-Hsp90 ribozyme reveals a complex mechanism of Hsp90 inhibitors involving both superoxide- and Hsp90-dependent events. J Biol Chem. 2003;278:35231–35240.
   PubMed Web of Science ®Google Scholar
• Dikalov S, Landmesser U, Harrison DG. Geldanamycin leads to superoxide formation by enzymatic and non-enzymatic redox cycling. Implications for studies of Hsp90 and endothelial cell nitric-oxide synthase. J Biol Chem. 2002;277:25480–25485.
   PubMed Web of Science ®Google Scholar
• Clark CB, Rane MJ, El Mehdi D, et al. Role of oxidative stress in geldanamycin-induced cytotoxicity and disruption of Hsp90 signaling complex. Free Radic Biol Med. 2009;47:1440–1449.
   PubMed Web of Science ®Google Scholar
• Zhang J, Liu W, Tan J, et al. Antifungal activity of geldanamycin alone or in combination with fluconazole against Candida species. Mycopathologia. 2013;175:273–279.
   PubMed Web of Science ®Google Scholar
• Robbins N, Uppuluri P, Nett J, et al. Hsp90 governs dispersion and drug resistance of fungal biofilms. PLOS Pathog. 2011;7:e1002257.
   PubMed Web of Science ®Google Scholar
• Cordeiro Rde A, Evangelista AJ, Serpa R, et al. Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex. Microbiology. 2016;162:309–317.
   PubMed Web of Science ®Google Scholar
• Shirazi F, Kontoyiannis DP. Heat shock protein 90 and calcineurin pathway inhibitors enhance the efficacy of triazoles against Scedosporium prolificans via induction of apoptosis. Microb Cell. 2014;1:179–188.
   PubMedGoogle Scholar
• O’Meara TR, Robbins N, Cowen LE. The Hsp90 chaperone network modulates candida virulence traits. Trends Microbiol. 2017;25:809–819.
   PubMed Web of Science ®Google Scholar
• Lamoth F, Juvvadi PR, Steinbach WJ. Heat shock protein 90 (Hsp90): a novel antifungal target against Aspergillus fumigatus. Crit Rev Microbiol. 2016;42(2):310–321.
   PubMed Web of Science ®Google Scholar
• Lamoth F, Juvvadi PR, Soderblom EJ, et al. Identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 2014;58:1889–1896.
   PubMed Web of Science ®Google Scholar
• Li L, An M, Shen H, et al. The non-geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole. Am J Transl Res. 2015;7:2589–2602.
   PubMed Web of Science ®Google Scholar
• Cowen LE, Lindquist S. Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science. 2005;309:2185–2189.
   PubMed Web of Science ®Google Scholar
• Kim Y, Alarcon S, Lee S, et al. Update on Hsp90 inhibitors in clinical trial. Curr Top Med Chem. 2009;9:1479–1492.
   PubMed Web of Science ®Google Scholar
• Jia C, Yu Q, Xu N, et al. Role of TFP1 in vacuolar acidification, oxidative stress and filamentous development in Candida albicans. Fungal Genet Biol. 2014;71:58–67.
   PubMed Web of Science ®Google Scholar
• Dong Y, Yu Q, Chen Y, et al. The Ccz1 mediates the autophagic clearance of damaged mitochondria in response to oxidative stress in Candida albicans. Int J Biochem Cell Biol. 2015;69:41–51.
   PubMed Web of Science ®Google Scholar
• da Silva CR, de Andrade Neto JB, Sidrim JJC, et al. Synergistic effects of amiodarone and fluconazole on Candida tropicalis resistant to fluconazole. Antimicrob Agents Chemother. 2013;57:1691–1700.
   PubMed Web of Science ®Google Scholar
• Li L, Sun J, Xia S, et al. Mechanism of antifungal activity of antimicrobial peptide APP, a cell-penetrating peptide derivative, against Candida albicans: intracellular DNA binding and cell cycle arrest. Appl Microbiol Biotechnol. 2016;100:3245–3253.
   PubMed Web of Science ®Google Scholar
• Xie JL, Qin L, Miao Z, et al. The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation. Nat Commun. 2017;8:499.
   PubMed Web of Science ®Google Scholar
• Jia C, Zhang K, Zhang D, et al. Effects of disruption of PMC1 in the tfp1Δ/Δ mutant on calcium homeostasis, oxidative and osmotic stress resistance in Candida albicans. Mycopathologia. 2018;183:315–327.
   PubMed Web of Science ®Google Scholar
• Bhattacharya S, Sobel JD, White TC. A combination fluorescence assay demonstrates increased efflux pump activity as a resistance mechanism in azole-resistant vaginal Candida albicans isolates. Antimicrob Agents Chemother. 2016;60:5858–5866.
   PubMed Web of Science ®Google Scholar
• Samuni Y, Ishii H, Hyodo F, et al. Reactive oxygen species mediate hepatotoxicity induced by the Hsp90 inhibitor geldanamycin and its analogs. Free Radic Biol Med. 2010;48:1559–1563.
   PubMed Web of Science ®Google Scholar
• Marchi S, Giorgi C, Suski JM, et al. Mitochondria-Ros crosstalk in the control of cell death and aging. J Signal Transduct. 2012;2012:1.
   Google Scholar
• Dey A, Cederbaum AI. Geldanamycin, an inhibitor of Hsp90, potentiates cytochrome P4502E1-mediated toxicity in HepG2 cells. J Pharmacol Exp Ther. 2006;317:1391–1399.
   PubMed Web of Science ®Google Scholar
• Mcilwrath AJ, Brunton VG, Brown R. Cell-cycle arrest and p53 accumulation induced by geldanamycin in human ovarian tumour cells. Cancer Chemother Pharmacol. 1996;37:423–428.
   PubMed Web of Science ®Google Scholar
• Bedin M, Gaben AM, Saucier C, et al. Geldanamycin, an inhibitor of the chaperone activity of HSP90, induces MAPK-independent cell cycle arrest. Int J Cancer. 2004;109:643–652.
   PubMed Web of Science ®Google Scholar
• Chae S, Yun C, Um H, et al. Centrosome amplification and multinuclear phenotypes are induced by hydrogen peroxide. Exp Mol Med. 2005;37:482–487.
   PubMed Web of Science ®Google Scholar
• Lamoth F, Juvvadi PR, Gehrke C, et al. In vitro activity of calcineurin and heat shock protein 90 inhibitors against Aspergillus fumigatus azole- and echinocandin-resistant strains. Antimicrob Agents Chemother. 2013;57:1035–1039.
   PubMed Web of Science ®Google Scholar
• Kobayashi D, Kondo K, Uehara N, et al. Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect. Antimicrob Agents Chemother. 2002;46:3113–3117.
   PubMed Web of Science ®Google Scholar
• Neckers L, Kern A, Tsutsumi S. Hsp90 inhibitors disrupt mitochondrial homeostasis in cancer cells. Chem Biol. 2007;14:1204–1206.
   PubMedGoogle Scholar
• Senn H, Shapiro RS, Cowen LE. Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression in Candida albicans. Mol Biol Cell. 2012;23:268–283.
   PubMed Web of Science ®Google Scholar