2,238
Views
20
CrossRef citations to date
0
Altmetric
Review

Antifungal adjuvants: Preserving and extending the antifungal arsenal

, &
Pages 198-210 | Received 04 Apr 2016, Accepted 19 Jul 2016, Published online: 19 Aug 2016

References

  • Lai CC, Tan CK, Huang YT, Shao PL, Hsueh PR. Current challenges in the management of invasive fungal infections. J Infect Chemother 2008; 14:77-85; PMID:18622668; http://dx.doi.org/10.1007/s10156-007-0595-7
  • Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009; 23:525-30 10.1097/QAD.0b013e328322ffac; PMID:19182676; http://dx.doi.org/10.1097/QAD.0b013e328322ffac
  • Butts A, Krysan DJ. Antifungal drug discovery: something old and something new. PLoS Pathog 2012; 8:e1002870; PMID:22969422; http://dx.doi.org/10.1371/journal.ppat.1002870
  • Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 2007; 6:29-40; PMID:17159923; http://dx.doi.org/10.1038/nrd2201
  • Donovick R, Gold W, Pagano JF, Stout HA. Amphotericins A and B, antifungal antibiotics produced by a streptomycete. I. In vitro studies. Antibiot Annu 1955; 3:579-86; PMID:13355330
  • Vandevelde AG, Mauceri AA, Johnson JE, 3rd. 5-fluorocytosine in the treatment of mycotic infections. Ann Intern Med 1972; 77:43-51; PMID:4559539; http://dx.doi.org/10.7326/0003-4819-77-1-43
  • Normark S, Schonebeck J. In vitro studies of 5-fluorocytosine resistance in Candida albicans and Torulopsis glabrata. Antimicrob Agents Chemother 1972; 2:114-21; PMID:4597703; http://dx.doi.org/10.1128/AAC.2.3.114
  • Fromtling RA. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev 1988; 1:187-217; PMID:3069196; http://dx.doi.org/10.1128/CMR.1.2.187
  • Brüggemann RJM, Alffenaar J-WC, Blijlevens NMA, Billaud EM, Kosterink JGW, Verweij PE, Burger DM, Saravolatz LD. Clinical Relevance of the Pharmacokinetic Interactions of Azole Antifungal Drugs with Other Coadministered Agents. Clinical Infectious Diseases 2009; 48:1441-58; PMID:19361301; http://dx.doi.org/10.1086/598327
  • Denning DW. Echinocandins: a new class of antifungal. J Antimicrob Chemoth 2002; 49:889-91; http://dx.doi.org/10.1093/jac/dkf045
  • Cowen LE. Hsp90 orchestrates stress response signaling governing fungal drug resistance. PLoS Pathog 2009; 5:e1000471; PMID:19714223; http://dx.doi.org/10.1371/journal.ppat.1000471
  • Cannon RD, Lamping E, Holmes AR, Niimi K, Tanabe K, Niimi M, Monk BC. Candida albicans drug resistance – another way to cope with stress. Microbiology+ 2007; 153:3211-7; PMID:17906120
  • Cowen LE, Steinbach WJ. Stress, Drugs, and Evolution: the Role of Cellular Signaling in Fungal Drug Resistance. Eukaryotic Cell 2008; 7:747-64; PMID:18375617; http://dx.doi.org/10.1128/EC.00041-08
  • Lewis JS, 2nd, Graybill JR. Fungicidal versus Fungistatic: what's in a word? Expert Opin Pharmacother 2008; 9:927-35; PMID:18377336; http://dx.doi.org/10.1517/14656566.9.6.927
  • Sutak R, Lesuisse E, Tachezy J, Richardson DR. Crusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence. Trends Microbiol 2008; 16:261-8; PMID:18467097; http://dx.doi.org/10.1016/j.tim.2008.03.005
  • Almeida RS, Wilson D, Hube B. Candida albicans iron acquisition within the host. FEMS Yeast Res 2009; 9:1000-12; PMID:19788558; http://dx.doi.org/10.1111/j.1567-1364.2009.00570.x
  • Fiori A, Van Dijck P. Potent synergistic effect of doxycycline with fluconazole against Candida albicans is mediated by interference with iron homeostasis. Antimicrob Agents Chemother 2012; 56:3785-96; PMID:22564841; http://dx.doi.org/10.1128/AAC.06017-11
  • Ibrahim AS, Gebremariam T, French SW, Edwards JE, Jr., Spellberg B. The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis. J Antimicrob Chemother 2010; 65:289-92; PMID:19942619; http://dx.doi.org/10.1093/jac/dkp426
  • Kobayashi T, Kakeya H, Miyazaki T, Izumikawa K, Yanagihara K, Ohno H, Yamamoto Y, Tashiro T, Kohno S. Synergistic antifungal effect of lactoferrin with azole antifungals against Candida albicans and a proposal for a new treatment method for invasive candidiasis. Jpn J Infect Dis 2011; 64:292-6; PMID:21788703
  • Henry KW, Nickels JT, Edlind TD. Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother 2000; 44:2693-700; PMID:10991846; http://dx.doi.org/10.1128/AAC.44.10.2693-2700.2000
  • Edlind T, Smith L, Henry K, Katiyar S, Nickels J. Antifungal activity in Saccharomyces cerevisiae is modulated by calcium signalling. Mol Microbiol 2002; 46:257-68; PMID:12366848; http://dx.doi.org/10.1046/j.1365-2958.2002.03165.x
  • Cui J, Kaandorp JA, Sloot PM, Lloyd CM, Filatov MV. Calcium homeostasis and signaling in yeast cells and cardiac myocytes. FEMS Yeast Res 2009; 9:1137-47; PMID:19678847; http://dx.doi.org/10.1111/j.1567-1364.2009.00552.x
  • Shi W, Chen Z, Chen X, Cao L, Liu P, Sun S. The combination of minocycline and fluconazole causes synergistic growth inhibition against Candida albicans: an in vitro interaction of antifungal and antibacterial agents. FEMS Yeast Res 2010; 10:885-93; PMID:20707818; http://dx.doi.org/10.1111/j.1567-1364.2010.00664.x
  • Liu S, Yue L, Gu W, Li X, Zhang L, Sun S. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans. PLoS One 2016; 11:e0150859; PMID:26986478; http://dx.doi.org/10.1371/journal.pone.0150859
  • Gamarra S, Rocha EM, Zhang YQ, Park S, Rao R, Perlin DS. Mechanism of the synergistic effect of amiodarone and fluconazole in Candida albicans. Antimicrob Agents Chemother 2010; 54:1753-61; PMID:20194694; http://dx.doi.org/10.1128/AAC.01728-09
  • Steinbach WJ, Reedy JL, Cramer RA, Jr., Perfect JR, Heitman J. Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat Rev Microbiol 2007; 5:418-30; PMID:17505522; http://dx.doi.org/10.1038/nrmicro1680
  • Clipstone NA, Crabtree GR. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 1992; 357:695-7; PMID:1377362; http://dx.doi.org/10.1038/357695a0
  • Hemenway CS, Heitman J. Calcineurin. Structure, function, and inhibition. Cell Biochem Biophys 1999; 30:115-51; PMID:10099825; http://dx.doi.org/10.1007/BF02737887
  • Blankenship JR. Calcineurin is essential for Candida albicans survival in serum and virulence. Eukaryot Cell 2003; 2:422-30; PMID:12796287; http://dx.doi.org/10.1128/EC.2.3.422-430.2003
  • Cruz MC. Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO J 2002; 21:546-59; PMID:11847103; http://dx.doi.org/10.1093/emboj/21.4.546
  • Onyewu C, Blankenship JR, Del Poeta M, Heitman J. Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrob Agents Chemother 2003; 47:956-64; PMID:12604527; http://dx.doi.org/10.1128/AAC.47.3.956-964.2003
  • Odom A. Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J 1997; 16:2576-89; PMID:9184205; http://dx.doi.org/10.1093/emboj/16.10.2576
  • Odom A, Del Poeta M, Perfect J, Heitman J. The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein. Antimicrob Agents Chemother 1997; 41:156-61; PMID:8980772
  • Del Poeta M, Cruz MC, Cardenas ME, Perfect JR, Heitman J. Synergistic Antifungal Activities of Bafilomycin A1, Fluconazole, and the Pneumocandin MK-0991/Caspofungin Acetate (L-743,873) with Calcineurin Inhibitors FK506 and L-685,818 against Cryptococcus neoformans. Antimicrob Agents Chemother 2000; 44:739-46; PMID:10681348; http://dx.doi.org/10.1128/AAC.44.3.739-746.2000
  • Bicanic T, Muzoora C, Brouwer AE, Meintjes G, Longley N, Taseera K, Rebe K, Loyse A, Jarvis J, Bekker LG, et al. Independent association between rate of clearance of infection and clinical outcome of HIV-associated cryptococcal meningitis: analysis of a combined cohort of 262 patients. Clin Infect Dis 2009; 49:702-9; PMID:19613840; http://dx.doi.org/10.1086/604716
  • Steinbach WJ. Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryot Cell 2006; 5:1091-103; PMID:16835453; http://dx.doi.org/10.1128/EC.00139-06
  • Kontoyiannis DP, Lewis RE, Osherov N, Albert ND, May GS. Combination of caspofungin with inhibitors of the calciuneurin pathway attenuates growth in vitro in Aspergillus species. J Antimicrob Chemother 2003; 51:313-6; PMID:12562696; http://dx.doi.org/10.1093/jac/dkg090
  • Steinbach WJ. In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus. Antimicrob Agents Chemother 2004; 48:1664-9; PMID:15105118; http://dx.doi.org/10.1128/AAC.48.5.1664-1669.2004
  • Reedy JL. Immunotherapy with tacrolimus (FK506) does not select for resistance to calcineurin inhibitors in Candida albicans isolates from liver transplant patients. Antimicrob Agents Chemother 2006; 50:1573-7; PMID:16569889; http://dx.doi.org/10.1128/AAC.50.4.1573-1577.2006
  • Blankenship JR, Singh N, Alexander BD, Heitman J. Cryptococcus neoformans isolates from transplant recipients are not selected for resistance to calcineurin inhibitors by current immunosuppressive regimens. J Clin Microbiol 2005; 43:464-7; PMID:15635017; http://dx.doi.org/10.1128/JCM.43.1.464-467.2005
  • Steinbach WJ. In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus isolates from transplant and nontransplant patients. Antimicrob Agents Chemother 2004; 48:4922-5; PMID:15561883; http://dx.doi.org/10.1128/AAC.48.12.4922-4925.2004
  • Dolan K, Montgomery S, Buchheit B, Didone L, Wellington M, Krysan DJ. Antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization. Antimicrob Agents Chemother 2009; 53:3337-46; PMID:19487443; http://dx.doi.org/10.1128/AAC.01564-08
  • Butts A, DiDone L, Koselny K, Baxter BK, Chabrier-Rosello Y, Wellington M, Krysan DJ. A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis. Eukaryot Cell 2013; 12:278-87; PMID:23243064; http://dx.doi.org/10.1128/EC.00314-12
  • Butts A, Koselny K, Chabrier-Roselló Y, Semighini CP, Brown JCS, Wang X, Annadurai S, DiDone L, Tabroff J, Childers WE, et al. Estrogen Receptor Antagonists Are Anti-Cryptococcal Agents That Directly Bind EF Hand Proteins and Synergize with Fluconazole In Vivo. MBio 2014; 5:e00765-13; PMID:24520056; http://dx.doi.org/10.1128/mBio.00765-13
  • Cowen LE, Carpenter AE, Matangkasombut O, Fink GR, Lindquist S. Genetic architecture of Hsp90-dependent drug resistance. Eukaryot Cell 2006; 5:2184-8; PMID:17056742; http://dx.doi.org/10.1128/EC.00274-06
  • Cowen LE, Lindquist S. Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 2005; 309:2185-9; PMID:16195452; http://dx.doi.org/10.1126/science.1118370
  • Cowen LE, Singh SD, Kohler JR, Collins C, Zaas AK, Schell WA, Aziz H, Mylonakis E, Perfect JR, Whitesell L, et al. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc Natl Acad Sci U S A 2009; 106:2818-23; PMID:19196973; http://dx.doi.org/10.1073/pnas.08133-94106
  • Lass-Florl C, Dierich MP, Fuchs D, Semenitz E, Ledochowski M. Antifungal activity against Candida species of the selective serotonin-reuptake inhibitor, sertraline. Clin Infect Dis 2001; 33:E135-6; PMID:11700578; http://dx.doi.org/10.1086/324589
  • Lass-Florl C, Dierich MP, Fuchs D, Semenitz E, Jenewein I, Ledochowski M. Antifungal properties of selective serotonin reuptake inhibitors against Aspergillus species in vitro. J Antimicrob Chemother 2001; 48:775-9; PMID:11733460; http://dx.doi.org/10.1093/jac/48.6.775
  • Spitzer M, Griffiths E, Blakely KM, Wildenhain J, Ejim L, Rossi L, De Pascale G, Curak J, Brown E, Tyers M, et al. Cross-species discovery of syncretic drug combinations that potentiate the antifungal fluconazole. Mol Syst Biol 2011; 7:499; PMID:21694716; http://dx.doi.org/10.1038/msb.2011.31
  • Robbins N, Spitzer M, Yu T, Cerone Robert P, Averette Anna K, Bahn Y-S, Heitman J, Sheppard Donald C, Tyers M, Wright Gerard D. An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens. Cell Reports 13:1481-92; PMID:26549450; http://dx.doi.org/10.1016/j.celrep.2015.10.018
  • Zhai B, Wu C, Wang L, Sachs MS, Lin X. The antidepressant sertraline provides a promising therapeutic option for neurotropic cryptococcal infections. Antimicrob Agents Chemother 2012; 56:3758-66; PMID:22508310; http://dx.doi.org/10.1128/AAC.00212-12
  • Rhein J, Morawski BM, Hullsiek KH, Nabeta HW, Kiggundu R, Tugume L, Musubire A, Akampurira A, Smith KD, Alhadab A, et al. Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study. Lancet Infect Dis 2016; 16:809-18; PMID:26971081; http://dx.doi.org/10.1016/S1473-3099(16)00074-8
  • Lorenz RT, Parks LW. Effects of lovastatin (mevinolin) on sterol levels and on activity of azoles in Saccharomyces cerevisiae. Antimicrob Agents Chemother 1990; 34:1660-5; PMID:2285278; http://dx.doi.org/10.1128/AAC.34.9.1660
  • Song JL, Lyons CN, Holleman S, Oliver BG, White TC. Antifungal activity of fluconazole in combination with lovastatin and their effects on gene expression in the ergosterol and prenylation pathways in Candida albicans. Med Mycol 2003; 41:417-25; PMID:14653518; http://dx.doi.org/10.1080/1369378031000137233
  • Nyilasi I, Kocsube S, Krizsan K, Galgoczy L, Pesti M, Papp T, Vagvolgyi C. In vitro synergistic interactions of the effects of various statins and azoles against some clinically important fungi. FEMS Microbiol Lett 2010; 307:175-84; PMID:20636975; http://dx.doi.org/10.1111/j.1574-6968.2010.01972.x
  • Noverr MC, Phare SM, Toews GB, Coffey MJ, Huffnagle GB. Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins. Infect Immun 2001; 69:2957-63; PMID: 11292712; http://dx.doi.org/10.1128/IAI.69.5.2957-2963.2001
  • Scott EM, Tariq VN, McCrory RM. Demonstration of synergy with fluconazole and either ibuprofen, sodium salicylate, or propylparaben against Candida albicans in vitro. Antimicrob Agents Chemother 1995; 39:2610-4; PMID:8592988; http://dx.doi.org/10.1128/AAC.39.12.2610
  • Pina-Vaz C, Sansonetty F, Rodrigues AG, Martinez-De-Oliveira J, Fonseca AF, Mardh PA. Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species. J Med Microbiol 2000; 49:831-40; PMID:10966233; http://dx.doi.org/10.1099/0022-1317-49-9-831
  • Guo N, Liu J, Wu X, Bi X, Meng R, Wang X, Xiang H, Deng X, Yu L. Antifungal activity of thymol against clinical isolates of fluconazole-sensitive and -resistant Candida albicans. J Med Microbiol 2009; 58:1074-9; PMID:19528168; http://dx.doi.org/10.1099/jmm.0.008052-0
  • Faria NC, Kim JH, Goncalves LA, Martins Mde L, Chan KL, Campbell BC. Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus. Lett Appl Microbiol 2011; 52:506-13; PMID:21332761; http://dx.doi.org/10.1111/j.1472-765X.2011.03032.x
  • Kim J, Campbell B, Mahoney N, Chan K, Molyneux R, May G. Chemosensitization prevents tolerance of Aspergillus fumigatus to antimycotic drugs. Biochem Biophys Res Commun 2008; 372:266-71; PMID:18486603; http://dx.doi.org/10.1016/j.bbrc.2008.05.030
  • Pinto E, Pina-Vaz C, Salgueiro L, Goncalves MJ, Costa-de-Oliveira S, Cavaleiro C, Palmeira A, Rodrigues A, Martinez-de-Oliveira J. Antifungal activity of the essential oil of Thymus pulegioides on Candida, Aspergillus and dermatophyte species. J Med Microbiol 2006; 55:1367-73; PMID:17005785; http://dx.doi.org/10.1099/jmm.0.46443-0
  • Ahmad A, Khan A, Khan LA, Manzoor N. In vitro synergy of eugenol and methyleugenol with fluconazole against clinical Candida isolates. J Med Microbiol 2010; 59:1178-84; PMID:20634332; http://dx.doi.org/10.1099/jmm.0.020693-0
  • Ahmad A, Khan A, Yousuf S, Khan LA, Manzoor N. Proton translocating ATPase mediated fungicidal activity of eugenol and thymol. Fitoterapia 2010; 81:1157-62; PMID:20659536; http://dx.doi.org/10.1016/j.fitote.20-10.07.020
  • Iwazaki RS, Endo EH, Ueda-Nakamura T, Nakamura CV, Garcia LB, Filho BP. In vitro antifungal activity of the berberine and its synergism with fluconazole. Antonie Van Leeuwenhoek 2010; 97:201-5; PMID:19882381; http://dx.doi.org/10.1007/s10482-009-9394-8
  • Sharma M, Manoharlal R, Negi AS, Prasad R. Synergistic anticandidal activity of pure polyphenol curcumin I in combination with azoles and polyenes generates reactive oxygen species leading to apoptosis. FEMS Yeast Res 2010; 10:570-8; PMID:20528949
  • Bang KH, Lee DW, Park HM, Rhee YH. Inhibition of fungal cell wall synthesizing enzymes by trans-cinnamaldehyde. Biosci Biotechnol Biochem 2000; 64:1061-3; PMID:10879482; http://dx.doi.org/10.1271/bbb.64.1061
  • Borjihan H, Ogita A, Fujita K, Hirasawa E, Tanaka T. The vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans and its enhancement by allicin. J Antibiot (Tokyo) 2009; 62:691-7; PMID:19876074; http://dx.doi.org/10.1038/ja.2009.103
  • Guo N, Wu X, Yu L, Liu J, Meng R, Jin J, Lu H, Wang X, Yan S, Deng X. In vitro and in vivo interactions between fluconazole and allicin against clinical isolates of fluconazole-resistant Candida albicans determined by alternative methods. FEMS Immunol Med Microbiol 2010; 58:193-201; PMID:19878317; http://dx.doi.org/10.1111/j.1574-695X.2009.00620.x
  • Han Y. Synergic anticandidal effect of epigallocatechin-O-gallate combined with amphotericin B in a murine model of disseminated candidiasis and its anticandidal mechanism. Biol Pharm Bull 2007; 30:1693-6; PMID:17827722; http://dx.doi.org/10.1248/bpb.30.1693
  • Schubert S, Barker KS, Znaidi S, Schneider S, Dierolf F, Dunkel N, Aid M, Boucher G, Rogers PD, Raymond M, et al. Regulation of efflux pump expression and drug resistance by the transcription factors Mrr1, Upc2, and Cap1 in Candida albicans. Antimicrob Agents Chemother 2011; 55:2212-23; PMID:21402859; http://dx.doi.org/10.1128/AAC.01343-10
  • White TC. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. Antimicrob Agents Chemother 1997; 41:1482-7; PMID:9210670
  • Revankar SG, Kirkpatrick WR, McAtee RK, Fothergill AW, Redding SW, Rinaldi MG, Patterson TF. Interpretation of trailing endpoints in antifungal susceptibility testing by the National Committee for Clinical Laboratory Standards method. J Clin Microbiol 1998; 36:153-6; PMID:9431939
  • Smith WL, Edlind TD. Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals: correlation with reduction in CDR and ERG upregulation. Antimicrob Agents Chemother 2002; 46:3532-9; PMID:12384361; http://dx.doi.org/10.1128/AAC.46.11.3532-3539.2002
  • Flowers SA, Barker KS, Berkow EL, Toner G, Chadwick SG, Gygax SE, Morschhauser J, Rogers PD. Gain-of-function mutations in UPC2 are a frequent cause of ERG11 upregulation in azole-resistant clinical isolates of Candida albicans. Eukaryot Cell 2012; 11:1289-99; PMID:22923048; http://dx.doi.org/10.1128/EC.00215-12
  • Del Sorbo G, Schoonbeek H, De Waard MA. Fungal transporters involved in efflux of natural toxic compounds and fungicides. Fungal Genet Biol 2000; 30:1-15; PMID:10955904; http://dx.doi.org/10.1006/fgbi.2000.1206
  • Schuetzer-Muehlbauer M, Willinger B, Egner R, Ecker G, Kuchler K. Reversal of antifungal resistance mediated by ABC efflux pumps from Candida albicans functionally expressed in yeast. Int J Antimicrob Agents 2003; 22:291-300; PMID:13678837; http://dx.doi.org/10.1016/S0924-8579(03)00213-9
  • Lee MD, Galazzo JL, Staley AL, Lee JC, Warren MS, Fuernkranz H, Chamberland S, Lomovskaya O, Miller GH. Microbial fermentation-derived inhibitors of efflux-pump-mediated drug resistance. Farmaco 2001; 56:81-5; PMID:11347972; http://dx.doi.org/10.1016/S0014-827X(01)01002-3
  • Niimi K, Harding DR, Parshot R, King A, Lun DJ, Decottignies A, Niimi M, Lin S, Cannon RD, Goffeau A, et al. Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative. Antimicrob Agents Chemother 2004; 48:1256-71; PMID:15047528; http://dx.doi.org/10.1128/AAC.48.4.1256-1271.2004
  • Niimi K, Harding DR, Holmes AR, Lamping E, Niimi M, Tyndall JD, Cannon RD, Monk BC. Specific interactions between the Candida albicans ABC transporter Cdr1p ectodomain and a D-octapeptide derivative inhibitor. Mol Microbiol 2012; 85:747-67; PMID:22788839; http://dx.doi.org/10.1111/j.1365-2958.2012.08140.x
  • Keniya MV, Fleischer E, Klinger A, Cannon RD, Monk BC. Inhibitors of the Candida albicans Major Facilitator Superfamily Transporter Mdr1p Responsible for Fluconazole Resistance. PLoS One 2015; 10:e0126350; PMID:25951180; http://dx.doi.org/10.1371/journal.pone.0126350
  • Holmes AR, Keniya MV, Ivnitski-Steele I, Monk BC, Lamping E, Sklar LA, Cannon RD. The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates. Antimicrob Agents Chemother 2012; 56:1508-15; PMID:22203607; http://dx.doi.org/10.1128/AAC.05706-11
  • Ahmad A, Khan A, Manzoor N. Reversal of efflux mediated antifungal resistance underlies synergistic activity of two monoterpenes with fluconazole. Eur J Pharm Sci 2013; 48:80-6; PMID:23111348; http://dx.doi.org/10.1016/j.ejps.2012.09.016
  • Huang S, Cao YY, Dai BD, Sun XR, Zhu ZY, Cao YB, Wang Y, Gao PH, Jiang YY. In vitro synergism of fluconazole and baicalein against clinical isolates of Candida albicans resistant to fluconazole. Biol Pharm Bull 2008; 31:2234-6; PMID:19043205; http://dx.doi.org/10.1248/bpb.31.2234
  • Gao Y, Zhang C, Lu C, Liu P, Li Y, Li H, Sun S. Synergistic effect of doxycycline and fluconazole against Candida albicans biofilms and the impact of calcium channel blockers. FEMS Yeast Res 2013; 13:453-62; PMID:23577622; http://dx.doi.org/10.1111/1567-1364.12048
  • Uppuluri P, Nett J, Heitman J, Andes D. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms. Antimicrob Agents Chemother 2008; 52:1127-32; PMID:18180354; http://dx.doi.org/10.1128/AAC.01397-07
  • Alem MA, Douglas LJ. Effects of aspirin and other nonsteroidal anti-inflammatory drugs on biofilms and planktonic cells of Candida albicans. Antimicrob Agents Chemother 2004; 48:41-7; PMID:14693516; http://dx.doi.org/10.1128/AAC.48.1.41-47.2004
  • Zhou Y, Wang G, Li Y, Liu Y, Song Y, Zheng W, Zhang N, Hu X, Yan S, Jia J. In vitro interactions between aspirin and amphotericin B against planktonic cells and biofilm cells of Candida albicans and C. parapsilosis. Antimicrob Agents Chemother 2012; 56:3250-60; PMID:22391539; http://dx.doi.org/10.1128/AAC.06082-11
  • Khan MS, Ahmad I. Antibiofilm activity of certain phytocompounds and their synergy with fluconazole against Candida albicans biofilms. J Antimicrob Chemother 2012; 67:618-21; PMID:22167241; http://dx.doi.org/10.1093/jac/dkr512
  • Delattin N, De Brucker K, Vandamme K, Meert E, Marchand A, Chaltin P, Cammue BP, Thevissen K. Repurposing as a means to increase the activity of amphotericin B and caspofungin against Candida albicans biofilms. J Antimicrob Chemother 2014; 69:1035-44; PMID:24284780; http://dx.doi.org/10.1093/jac/dkt449
  • Campbell BC, Chan KL, Kim JH. Chemosensitization as a means to augment commercial antifungal agents. Front Microbiol 2012; 3:79; PMID:22393330
  • Liu S, Hou Y, Chen X, Gao Y, Li H, Sun S. Combination of fluconazole with non-antifungal agents: a promising approach to cope with resistant Candida albicans infections and insight into new antifungal agent discovery. Int J Antimicrob Agents 2014; 43:395-402; PMID:24503221; http://dx.doi.org/10.1016/j.ijantimicag.2013.12.009
  • Borisy AA, Elliott PJ, Hurst NW, Lee MS, Lehar J, Price ER, Serbedzija G, Zimmermann GR, Foley MA, Stockwell BR, et al. Systematic discovery of multicomponent therapeutics. Proc Natl Acad Sci U S A 2003; 100:7977-82; PMID:12799470; http://dx.doi.org/10.1073/pnas.1337-088100
  • Cui J, Ren B, Tong Y, Dai H, Zhang L. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans. Virulence 2015; 6:362-71; PMID:26048362; http://dx.doi.org/10.1080/21505594.2015.1039885
  • Coelho C, Casadevall A. Cryptococcal therapies and drug targets:the old, the new and the promising. Cell Microbiol 2016; 18(6):792-9; PMID:26990050

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.