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Use of Novel Tools to Probe Drug Resistance in Fungi

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Handbook of Antimicrobial Resistance

Abstract

Antifungal drug resistance threatens therapeutic effectiveness and needs to be diagnosed in a timely manner. Currently, recognition of antifungal resistance still relies on culture-based susceptibility testing. Yet, antifungal susceptibility testing is not routinely performed and often comes too late to influence a timely decision on patient management. With the quantum leap of molecular technology and accrued insights on basic fungal cell biology and antifungal drug resistance mechanisms, some novel molecular techniques are now available to provide a faster and more accurate assessment of both primary and secondary resistance than classical methodologies. Validated targets for echinocandin resistance in Candida spp . and triazole resistance in Aspergillus fumigatus and Candida spp. are particularly well suited for molecular detection. Yet, implementation of a molecular diagnosis for drug resistance into the clinical settings requires validation in well-designed clinical trials, as well as improved methods for highly efficient primary sample preparation.

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References

  • Alexander BD et al (2013) Increasing echinocandin resistance in candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 56:1724

    Article  PubMed  PubMed Central  Google Scholar 

  • Al-Wathiqi F, Ahmad S, Khan Z (2013) Molecular identification and antifungal susceptibility profile of Aspergillus flavus isolates recovered from clinical specimens in Kuwait. BMC Infect Dis 13:126

    Article  PubMed  PubMed Central  Google Scholar 

  • Antachopoulos C, Meletiadis J, Sein T, Roilides E, Walsh TJ (2008) Comparative in vitro pharmacodynamics of caspofungin, micafungin, and anidulafungin against germinated and nongerminated Aspergillus conidia. Antimicrob Agents Chemother 52:321

    Article  CAS  PubMed  Google Scholar 

  • Arendrup MC, Perkhofer S, Howard SJ, Garcia-Effron G, Vishukumar A, Perlin D, Lass-Florl C (2008) Establishing in vitro-in vivo correlations for Aspergillus fumigatus: the challenge of azoles versus echinocandins. Antimicrob Agents Chemother 52:3504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arendrup MC et al (2009) Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment: laboratory characteristics and implication for susceptibility testing. Antimicrob Agents Chemother 53:1185

    Article  CAS  PubMed  Google Scholar 

  • Arendrup MC et al (2010) Development of azole resistance in Aspergillus fumigatus during azole therapy associated with change in virulence. PLoS One 5:e10080

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arendrup MC, Perlin DS, Jensen RH, Howard SJ, Goodwin J, Hope W (2012) Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations. Antimicrob Agents Chemother 56:2435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arikan S, Lozano-Chiu M, Paetznick V, Rex JH (2001) In vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates. Antimicrob Agents Chemother 45:327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arikan-Akdagli S (2012) Azole resistance in Aspergillus: global status in Europe and Asia. Ann N Y Acad Sci 1272:9

    Article  CAS  PubMed  Google Scholar 

  • Balashov SV, Gardiner R, Park S, Perlin DS (2005) Rapid, high-throughput, multiplex, real-time PCR for identification of mutations in the cyp51A gene of Aspergillus fumigatus that confer resistance to itraconazole. J Clin Microbiol 43:214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balashov SV, Park S, Perlin DS (2006) Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1. Antimicrob Agents Chemother 50:2058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ben-Ami R, Garcia-Effron G, Lewis RE, Gamarra S, Leventakos K, Perlin DS, Kontoyiannis DP (2011) Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance. J Infect Dis 204:626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bowman JC, Hicks PS, Kurtz MB, Rosen H, Schmatz DM, Liberator PA, Douglas CM (2002) The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro. Antimicrob Agents Chemother 46:3001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bowyer P, Mosquera J, Anderson M, Birch M, Bromley M, Denning DW (2012) Identification of novel genes conferring altered azole susceptibility in Aspergillus fumigatus. FEMS Microbiol Lett 332:10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bueid A, Howard SJ, Moore CB, Richardson MD, Harrison E, Bowyer P, Denning DW (2010) Azole antifungal resistance in Aspergillus fumigatus: 2008 and 2009. J Antimicrob Chemother 65:2116

    Article  CAS  PubMed  Google Scholar 

  • Buied A, Moore CB, Denning DW, Bowyer P (2013) High-level expression of cyp51B in azole-resistant clinical Aspergillus fumigatus isolates. J Antimicrob Chemother 68:512

    Article  CAS  PubMed  Google Scholar 

  • Castanheira M, Woosley LN, Diekema DJ, Messer SA, Jones RN, Pfaller MA (2010) Low prevalence of fks1 hot spot 1 mutations in a worldwide collection of Candida strains. Antimicrob Agents Chemother 54:2655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chau AS, Mendrick CA, Sabatelli FJ, Loebenberg D, McNicholas PM (2004) Application of real-time quantitative PCR to molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles. Antimicrob Agents Chemother 48:2124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chowdhary A et al (2012) Clonal expansion and emergence of environmental multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR(3)(4)/L98H mutations in the cyp51A gene in India. PLoS One 7:e52871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • CLSI (2008a) CLSI document M28-A2. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  • CLSI (2008b) CLSI document M27-A3. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  • Coste A et al (2006) A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics 172:2139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Denning DW (2003) Echinocandin antifungal drugs. Lancet 362:1142

    Article  CAS  PubMed  Google Scholar 

  • Denning DW et al (2011) High-frequency triazole resistance found In nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis 52:1123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dhamgaye S et al (2012) RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans. BMC Genomics 13:396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ecker DJ et al (2010) New technology for rapid molecular diagnosis of bloodstream infections. Expert Rev Mol Diagn 10:399

    Article  CAS  PubMed  Google Scholar 

  • Espinel-Ingroff A (2003) Utility of mould susceptibility testing. Curr Opin Infect Dis 16:527

    Article  CAS  PubMed  Google Scholar 

  • Ferrari S, Sanguinetti M, Torelli R, Posteraro B, Sanglard D (2011) Contribution of CgPDR1-Regulated Genes in Enhanced Virulence of Azole-Resistant Candida glabrata. PLoS One 6: e17589

    Google Scholar 

  • Ferreira ME et al (2005) The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus. Med Mycol 43(Suppl 1):S313

    Article  PubMed  CAS  Google Scholar 

  • Ferreira JA, Carr JH, Starling CE, de Resende MA, Donlan RM (2009) Biofilm formation and effect of caspofungin on biofilm structure of Candida species bloodstream isolates. Antimicrob Agents Chemother 53:4377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flowers SA et al (2012) Gain-of-function mutations in UPC2 are a frequent cause of ERG11 upregulation in azole-resistant clinical isolates of Candida albicans. Eukaryot Cell 11:1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fraczek MG et al (2013) The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus. J Antimicrob Chemother 68:1486

    Google Scholar 

  • Fridkin SK, Jarvis WR (1996) Epidemiology of nosocomial fungal infections. Clin Microbiol Rev 9:499

    CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Effron G, Dilger A, Alcazar-Fuoli L, Park S, Mellado E, Perlin DS (2008) Rapid detection of triazole antifungal resistance in Aspergillus fumigatus. J Clin Microbiol 46:1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Effron G, Lee S, Park S, Cleary JD, Perlin DS (2009a) Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother 53:3690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Effron G, Park S, Perlin DS (2009b) Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. Antimicrob Agents Chemother 53:112

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Effron G, Chua DJ, Tomada JR, DiPersio J, Perlin DS, Ghannoum M, Bonilla H (2010) Novel FKS mutations associated with echinocandin resistance in Candida species. Antimicrob Agents Chemother 54:2225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gardiner RE, Souteropoulos P, Park S, Perlin DS (2005) Characterization of Aspergillus fumigatus mutants with reduced susceptibility to caspofungin. Med Mycol 43(Suppl 1):S299

    Article  CAS  PubMed  Google Scholar 

  • Geber A, Hitchcock CA, Swartz JE, Pullen FS, Marsden KE, Kwon-Chung KJ, Bennett JE (1995) Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility. Antimicrob Agents Chemother 39:2708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gygax SE et al (2008) Antifungal resistance of Candida glabrata vaginal isolates and development of a quantitative reverse transcription-PCR-based azole susceptibility assay. Antimicrob Agents Chemother 52:3424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heald AE, Cox GM, Schell WA, Bartlett JA, Perfect JR (1996) Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy. AIDS 10:263

    Article  CAS  PubMed  Google Scholar 

  • Henry KW, Nickels JT, Edlind TD (2000) Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother 44:2693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holmes AR et al (2008) ABC transporter Cdr1p contributes more than Cdr2p does to fluconazole efflux in fluconazole-resistant Candida albicans clinical isolates. Antimicrob Agents Chemother 52:3851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howard SJ et al (2009) Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 15:1068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howard SJ et al (2011) Pharmacodynamics of echinocandins against Candida glabrata: requirement for dosage escalation to achieve maximal antifungal activity in neutropenic hosts. Antimicrob Agents Chemother 55:4880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hull CM et al (2012) Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance to azoles and amphotericin B. Antimicrob Agents Chemother 56:4223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imhof A, Balajee SA, Marr KA (2003) New methods to assess susceptibilities of Aspergillus isolates to caspofungin. J Clin Microbiol 41:5683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karababa M, Coste AT, Rognon B, Bille J, Sanglard D (2004) Comparison of gene expression profiles of Candida albicans azole-resistant clinical isolates and laboratory strains exposed to drugs inducing multidrug transporters. Antimicrob Agents Chemother 48:3064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kartsonis N, DiNubile MJ, Bartizal K, Hicks PS, Ryan D, Sable CA (2002) Efficacy of caspofungin in the treatment of esophageal candidiasis resistant to fluconazole. J Acquir Immune Defic Syndr 31:183

    Article  CAS  PubMed  Google Scholar 

  • Katiyar S, Pfaller M, Edlind T (2006) Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility. Antimicrob Agents Chemother 50:2892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelly SL et al (1997) Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol delta5,6- desaturation. FEBS Lett 400:80

    Article  CAS  PubMed  Google Scholar 

  • Klaassen CH, de Valk HA, Curfs-Breuker IM, Meis JF (2010) Novel mixed-format real-time PCR assay to detect mutations conferring resistance to triazoles in Aspergillus fumigatus and prevalence of multi-triazole resistance among clinical isolates in the Netherlands. J Antimicrob Chemother 65:901

    Article  CAS  PubMed  Google Scholar 

  • Kofla G, Ruhnke M (2007) Development of a new real-time TaqMan PCR assay for quantitative analyses of Candida albicans resistance genes expression. J Microbiol Methods 68:178

    Article  CAS  PubMed  Google Scholar 

  • Landlinger C, Preuner S, Willinger B, Haberpursch B, Racil Z, Mayer J, Lion T (2009) Species-specific identification of a wide range of clinically relevant fungal pathogens by use of Luminex xMAP technology. J Clin Microbiol 47:1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lepak A, Castanheira M, Diekema D, Pfaller M, Andes D (2012) Optimizing Echinocandin dosing and susceptibility breakpoint determination via in vivo pharmacodynamic evaluation against Candida glabrata with and without fks mutations. Antimicrob Agents Chemother 56:5875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis RE, Liao G, Hou J, Prince RA, Kontoyiannis DP (2011) Comparative in vivo dose-dependent activity of caspofungin and anidulafungin against echinocandin-susceptible and -resistant Aspergillus fumigatus. J Antimicrob Chemother 66:1324

    Article  CAS  PubMed  Google Scholar 

  • Loeffler J, Hagmeyer L, Hebart H, Henke N, Schumacher U, Einsele H (2000a) Rapid detection of point mutations by fluorescence resonance energy transfer and probe melting curves in Candida species. Clin Chem 46:631

    CAS  PubMed  Google Scholar 

  • Loeffler J, Henke N, Hebart H, Schmidt D, Hagmeyer L, Schumacher U, Einsele H (2000b) Quantification of fungal DNA by using fluorescence resonance energy transfer and the light cycler system. J Clin Microbiol 38:586

    CAS  PubMed  PubMed Central  Google Scholar 

  • MacCallum DM, Coste A, Ischer F, Jacobsen MD, Odds FC, Sanglard D (2010) Genetic dissection of azole resistance mechanisms in Candida albicans and their validation in a mouse model of disseminated infection. Antimicrob Agents Chemother 54:1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martel CM et al (2010) Identification and characterization of four azole-resistant erg3 mutants of Candida albicans. Antimicrob Agents Chemother 54:4527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Modi DA, Farrell JJ, Sampath R, Bhatia NS, Massire C, Ranken R, Bonomo RA (2012) Rapid identification of Aspergillus terreus from Bronchoalverolar lavage fluid by PCR and Electrospray-Ionization with Mass Spectrometry (PCR/ESI-MS). J Clin Microbiol 50:2529

    Google Scholar 

  • Mogavero S, Tavanti A, Senesi S, Rogers PD, Morschhauser J (2011) Differential Requirement of the Transcription Factor Mcm1 for Activation of the Candida albicans Multidrug Efflux Pump MDR1 by Its Regulators Mrr1 and Cap1. Antimicrob Agents Chemother 55:2061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morio F, Loge C, Besse B, Hennequin C, Le Pape P (2010) Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature. Diagn Microbiol Infect Dis 66:373

    Article  CAS  PubMed  Google Scholar 

  • Morio F, Pagniez F, Lacroix C, Miegeville M, Le Pape P (2012) Amino acid substitutions in the Candida albicans sterol Delta5,6-desaturase (Erg3p) confer azole resistance: characterization of two novel mutants with impaired virulence. J Antimicrob Chemother 67:2131

    Article  CAS  PubMed  Google Scholar 

  • Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49:3640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrison VA (2006) Echinocandin antifungals: review and update. Expert Rev Anti Infect Ther 4:325

    Article  CAS  PubMed  Google Scholar 

  • Nagi M et al (2011) Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes in Candida glabrata. Genes Cells 16:80

    Article  CAS  PubMed  Google Scholar 

  • Nascimento AM et al (2003) Multiple Resistance Mechanisms among Aspergillus fumigatus Mutants with High-Level Resistance to Itraconazole. Antimicrob Agents Chemother 47:1719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oliver BG, Song JL, Choiniere JH, White TC (2007) cis-Acting elements within the Candida albicans ERG11 promoter mediate the azole response through transcription factor Upc2p. Eukaryot Cell 6:2231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pancholi P, Park S, Perlin D, Kubin C, Della-Latta P (2004) Molecular characterization of fluconazole resistance in a case of Candida albicans ocular infection. J Clin Microbiol 42:5938

    Article  PubMed  PubMed Central  Google Scholar 

  • Pappas PG et al (2007) Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis 45:883

    Article  CAS  PubMed  Google Scholar 

  • Park S, Perlin DS (2005) Establishing surrogate markers for fluconazole resistance in Candida albicans. Microb Drug Resist 11:232

    Article  CAS  PubMed  Google Scholar 

  • Park S et al (2000) Rapid identification of Candida dubliniensis using a species-specific molecular beacon. J Clin Microbiol 38:2829

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park S et al (2005) Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother 49:3264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perea S et al (2001) Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 45:2676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perlin DS (2007) Resistance to echinocandin-class antifungal drugs. Drug Resist Updat 10:121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perlin DS (2009) Antifungal drug resistance: do molecular methods provide a way forward? Curr Opin Infect Dis 22:568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perlin DS (2011) Current perspectives on echinocandin class drugs. Future Microbiol 6:441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfaller MA (2012) Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 125:S3

    Article  CAS  PubMed  Google Scholar 

  • Pfaller MA, Diekema DJ (2010) Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 36:1

    Article  PubMed  Google Scholar 

  • Pfaller MA et al (2007) Results from the ARTEMIS DISK Global Antifungal Surveillance study, 1997 to 2005: an 8.5-year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J Clin Microbiol 45:1735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfaller MA et al (2011) Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 14:164

    Article  CAS  PubMed  Google Scholar 

  • Pfaller MA, Castanheira M, Lockhart SR, Ahlquist AM, Messer SA, Jones RN (2012) Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Microbiol 50:1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Polakova S, Blume C, Zarate JA, Mentel M, Jorck-Ramberg D, Stenderup J, Piskur J (2009) Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata. Proc Natl Acad Sci U S A 106:2688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rautemaa R, Richardson M, Pfaller M, Koukila-Kahkola P, Perheentupa J, Saxen H (2007) Decreased susceptibility of Candida albicans to azole antifungals: a complication of long-term treatment in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients. J Antimicrob Chemother 60:889

    Article  CAS  PubMed  Google Scholar 

  • Rex JH, Rinaldi MG, Pfaller MA (1995) Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 39:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rocha EM, Garcia-Effron G, Park S, Perlin DS (2007) A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. Antimicrob Agents Chemother 51:4174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanglard D, Odds FC (2002) Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect Dis 2:73

    Article  CAS  PubMed  Google Scholar 

  • Sanguinetti M, Posteraro B, Fiori B, Ranno S, Torelli R, Fadda G (2005) Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob Agents Chemother 49:668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schubert S et al (2011) Regulation of Efflux Pump Expression and Drug Resistance by the Transcription Factors Mrr1, Upc2, and Cap1 in Candida albicans. Antimicrob Agents Chemother 55:2212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selmecki A, Forche A, Berman J (2006) Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313:367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shields RK, Nguyen MH, Press EG, Kwa AL, Cheng S, Du C, Clancy CJ (2012) The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata. Antimicrob Agents Chemother 56:4862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slater JL et al (2011) Disseminated Candidiasis caused by Candida albicans with amino acid substitutions in Fks1 at position Ser645 cannot be successfully treated with micafungin. Antimicrob Agents Chemother 55:3075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slaven JW, Anderson MJ, Sanglard D, Dixon GK, Bille J, Roberts IS, Denning DW (2002) Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet Biol 36:199

    Article  CAS  PubMed  Google Scholar 

  • Snelders E, Huis In’t Veld RA, Rijs AJ, Kema GH, Melchers WJ, Verweij PE (2009) Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles. Appl Environ Microbiol 75:4053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST) (2008a) EUCAST definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. Clin Microbiol Infect 14:398

    Google Scholar 

  • Subcommittee on Antifungal Susceptibility Testing of the ESCMID European Committee for Antimicrobial Susceptibility Testing (2008b) EUCAST Technical Note on the method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia-forming moulds. Clin Microbiol Infect 14:982

    Google Scholar 

  • Vermitsky JP, Edlind TD (2004) Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrob Agents Chemother 48:3773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verweij PE, Mellado E, Melchers WJ (2007) Multiple-triazole-resistant aspergillosis. N Engl J Med 356:1481

    Article  CAS  PubMed  Google Scholar 

  • Verweij PE, Howard SJ, Melchers WJ, Denning DW (2009a) Azole-resistance in Aspergillus: proposed nomenclature and breakpoints. Drug Resist Updat 12:141

    Article  CAS  PubMed  Google Scholar 

  • Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ (2009b) Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis 9:789

    Article  CAS  PubMed  Google Scholar 

  • Walsh TJ et al (2008) Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46:327

    Article  CAS  PubMed  Google Scholar 

  • Wellinghausen N, Siegel D, Winter J, Gebert S (2009) Rapid diagnosis of candidaemia by real-time PCR detection of Candida DNA in blood samples. J Med Microbiol 58:1106

    Article  CAS  PubMed  Google Scholar 

  • White TC, Holleman S, Dy F, Mirels LF, Stevens DA (2002) Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob Agents Chemother 46:1704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiederhold NP, Lewis RE (2003) The echinocandin antifungals: an overview of the pharmacology, spectrum and clinical efficacy. Expert Opin Investig Drugs 12:1313

    Article  CAS  PubMed  Google Scholar 

  • Wiederhold NP, Najvar LK, Bocanegra RA, Kirkpatrick WR, Patterson TF (2011) Caspofungin dose escalation for invasive candidiasis due to resistant Candida albicans. Antimicrob Agents Chemother 55:3254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolk DM, Kaleta EJ, Wysocki VH (2012) PCR-Electrospray Ionization Mass Spectrometry: The Potential to Change Infectious Disease Diagnostics in Clinical and Public Health Laboratories. J Mol Diagn 14:295

    Google Scholar 

  • Yan L et al (2008) DNA microarray analysis of fluconazole resistance in a laboratory Candida albicans strain. Acta Biochim Biophys Sin (Shanghai) 40:1048

    Article  CAS  Google Scholar 

  • Zhao Y, Stensvold CR, Perlin DS, Arendrup MC (2013) Azole resistance in Aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases. J Antimicrob Chemother 68:1497

    Google Scholar 

  • Zimbeck AJ, Iqbal N, Ahlquist AM, Farley MM, Harrison LH, Chiller T, Lockhart SR (2010) FKS mutations and elevated echinocandin MIC values among Candida glabrata isolates from U.S. population-based surveillance. Antimicrob Agents Chemother 54:5042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ, 07103, USA

    Yanan Zhao & David S. Perlin

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  2. David S. Perlin
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Correspondence to David S. Perlin .

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Editors and Affiliations

  1. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Albert Berghuis

  2. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Greg Matlashewski

  3. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Mark A. Wainberg

  4. Department of Microbiology and Immunology, McGill University, Montreal, Québec, Canada

    Donald Sheppard

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Zhao, Y., Perlin, D.S. (2017). Use of Novel Tools to Probe Drug Resistance in Fungi. In: Berghuis, A., Matlashewski, G., Wainberg, M., Sheppard, D. (eds) Handbook of Antimicrobial Resistance. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0694-9_21

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