Skip to main content
SpringerLink
Log in

Human Fungal Pathogens and Drug Resistance Against Azole Drugs

  • Chapter
  • First Online:
Drug Resistance in Bacteria, Fungi, Malaria, and Cancer

Abstract

Pathogenic fungi causing severe infections in humans with immunocompromised immune system have been the major reasons of deaths in the world. Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus are among the most prevalent human fungal pathogens. The most widely used therapy used for the invasive fungal infections is the treatment with azole antifungal drugs; however, drug resistance against azole drugs is a major limitation in treatment of fungal infections. High-throughput techniques such as genomics and proteomics have been applied to understand the molecular mechanisms involved in drug resistance against azole drugs in human pathogenic fungi. These studies could be useful to prevent the increase in drug resistance and better response to antifungals. Here, we focus on the incidences of drug resistance against azole antifungal drugs in human fungal pathogens, molecular mechanisms of drug resistance, and new strategies for combating drug resistance to improve clinical treatment of invasive fungal infections.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agarwal AK, Rogers PD, Baerson SR, Jacob MR, Barker KS, Cleary JD, Walker LA, Nagle DG, Clark AM (2003) Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae. J Biol Chem 278:34998–35015. doi:10.1074/jbc.M306291200

    Article  CAS  PubMed  Google Scholar 

  • Alastruey-Izquierdo A, Mellado E, Peláez T, Pemán J, Zapico S, Alvarez M, Rodríguez-Tudela JL, Cuenca-Estrella M (2013) Population-based survey of filamentous fungi and antifungal resistance in Spain (FILPOP Study). Antimicrob Agents Chemother 57:3380–3387. doi:10.1128/AAC.00383-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ally R, Schürmann D, Kreisel W, Carosi G, Aguirrebengoa K, Dupont B, Hodges M, Troke P, Romero AJ, Esophageal Candidiasis Study Group (2001) A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis 33:1447–1454. doi:10.1086/322653

    Article  CAS  PubMed  Google Scholar 

  • Al-mamari A, Al-buryhi M, Al-heggami MA, Al-hag S (2014) Identify and sensitivity to antifungal drugs of Candida species causing vaginitis isolated from vulvovaginal infected patients in Sana’a city. Der Pharma Chemica 6:336–342

    Google Scholar 

  • Al-Mohsen I, Hughes WT (1998) Systemic antifungal therapy: past, present and future. Ann Saudi Med 18:28–38

    CAS  PubMed  Google Scholar 

  • Amitani R, Taylor G, Elezis EN, Llewellyn-Jones C, Mitchell J, Kuze F, Cole PJ, Wilson R (1995) Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium. Infect Immun 63:3266–3271

    CAS  PubMed  PubMed Central  Google Scholar 

  • Andriole VT (1998) Current and future therapy of invasive fungal infections. In: Remington J, Swartz M (eds) Current clinical topics in infections diseases. Blackwell Sciences, Malden, pp 19–36

    Google Scholar 

  • Andriole VT (1999) The 1998 Garrod Plecture. Current and future antifungal therapy:new targets for antifungal agents. J Antimicrob Chemother 44:151–162. doi:10.1093/jac/44.2.151

    Article  CAS  PubMed  Google Scholar 

  • Andriole VT, Bodey GP (1994) Pocket guide to systemic antifungal therapy. Scientific Therapeutics, Madison, NJ, 148 p

    Google Scholar 

  • Andriole VT, Kravetz HM (1962) The use of amphotericin B in man. JAMA 180:269–272

    Article  CAS  PubMed  Google Scholar 

  • Arendrup MC, Dzajic E, Jensen RH, Johansen HK, Kjaeldgaard P, Knudsen JD, Kristensen L, Leitz C, Lemming LE, Nielsen L, Olesen B, Rosenvinge FS, Røder BL, Schønheyder HC (2013) Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme. Clin Microbiol Infect 19:E343–E353. doi:10.1111/1469-0691.12212

    Article  CAS  PubMed  Google Scholar 

  • Bader O, Weig M, Reichard U, Lugert R, Kuhns M, Christner M, Held J, Peter S, Schumacher U, Buchheidt D, Tintelnot K, Groß U, Partners MLN-D (2013) cyp51A-Based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany. Antimicrob Agents Chemother 57:3513–3517. doi:10.1128/AAC.00167-13

    Article  CAS  PubMed  PubMed Central  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 43:214–222. doi:10.1128/JCM.43.1.214-222.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bennett JW, Klich M (2003) Mycotoxins. Clin Microbiol Rev 16:497–516. doi:10.1128/CMR.16.3.497-516.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ben-Yaacov R, Knoller S, Caldwell GA, Becker JM, Koltin Y (1994) Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene. Antimicrob Agents Chemother 38:648–652. doi:10.1128/AAC.38.4.648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breger J, Fuchs BB, Aperis G, Moy TI, Ausubel FM, Mylonakis E (2007) Antifungal chemical compounds identified using a C. elegans pathogenicity assay. PLoS Pathog 3, e18. doi:10.1371/journal.ppat.0030018

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Camps SM, Dutilh BE, Arendrup MC, Rijs AJ, Snelders E, Huynen MA, Verweij PE, Melchers WJ (2012) Discovery of a HapE mutation that causes azole resistance in Aspergillus fumigatus through whole genome sequencing and sexual crossing. PLoS One 7, e50034. doi:10.1371/journal

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang CC, Ananda-Rajah M, Belcastro A, McMullan B, Reid A, Dempsey K, Athan E, Cheng AC, Slavin MA (2014) Consensus guidelines for implementation of quality processes to prevent invasive fungal disease and enhanced surveillance measures during hospital building works. Intern Med J 44:1389–1397. doi:10.1111/imj.12601

    Article  CAS  PubMed  Google Scholar 

  • Chen CG, Yang YL, Shih HI, Su CL, Lo HJ (2004) CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1. Antimicrob Agents Chemother 48:4505–4512. doi:10.1128/AAC.48.12.4505-4512.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coleman JJ, Mylonakis E (2009) Efflux in fungi:la pièce de résistance. PLoS Pathog 5, e1000486. doi:10.1371/journal.ppat.1000486

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Costa C, Dias PJ, Sá-Correia I, Teixeira MC (2014) MFS multidrug transporters in pathogenic fungi: do they have real clinical impact? Front Physiol 5:197. doi:10.3389/fphys.2014.00197

    PubMed  PubMed Central  Google Scholar 

  • Coste A, Selmecki A, Forche A, Diogo D, Bougnoux ME, d’Enfert C, Berman J, Sanglard D (2007) Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot Cell 6:1889–1904. doi:10.1128/EC.00151-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coste AT, Crittin J, Bauser C, Rohde B, Sanglard D (2009) Functional analysis of cis-and trans-acting elements of the Candida albicans CDR2 promoter with a novel promoter reporter system. Eukaryot Cell 8:1250–1267. doi:10.1128/EC.00069-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cowen LE (2009) Hsp90 orchestrates stress response signaling governing fungal drug resistance. PLoS Pathog 8, e1000471. doi:10.1371/journal.ppat.1000471

    Article  CAS  Google Scholar 

  • Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Buitrago MJ, Monzon A, Rodriguez-Tudela JL (2006) Head-to-head comparison of the activities of currently available antifungal agents against 3,378 Spanish clinical isolates of yeasts and filamentous fungi. Antimicrob Agents Chemother 50:917–921. doi:10.1128/AAC.50.3.917-921.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • d’Enfert C (2009) Hidden killers: persistence of opportunistic fungal pathogens in the human host. Curr Opin Microbiol 12:358–364. doi:10.1016/j.mib.2009.05.008

    Article  PubMed  Google Scholar 

  • da Silva Ferreira ME, Malavazi I, Savoldi M, Brakhage AA, Goldman MH, Kim HS, Nierman WC, Goldman GH (2006) Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole. Curr Genet 50:32–44

    Article  PubMed  CAS  Google Scholar 

  • Dagenais TR, Keller NP (2009) Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin Microbiol Rev 22:447–465. doi:10.1128/CMR.00055-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Micheli M, Bille J, Schueller C, Sanglard D (2002) A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance. Mol Microbiol 43:1197–1214. doi:10.1046/j.1365-2958.2002.02814.x

    Article  PubMed  Google Scholar 

  • Denning DW, Venkateswarlu K, Oakley KL, Anderson MJ, Manning NJ, Stevens DA, Warnock DW, Kelly SL (1997) Itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 41:1364–1368

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dhamgaye S, Bernard M, Lelandais G, Sismeiro O, Lemoine S, Coppée JY, Le Crom S, Prasad R, Devaux F (2012) RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans. BMC Genomics 13:396. doi:10.1186/1471-2164-13-396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diaz-Guerra TM, Mellado E, Cuenca-Estrella M, Rodriguez-Tudela JL (2003) A point mutation in the 14-alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in A. fumigatus. Antimicrob Agents Chemother 47:1120–1124. doi:10.1128/AAC.47.3.1120-1124.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dirr F, Echtenacher B, Heesemann J, Hoffmann P, Ebel F, Wagener J (2010) AfMkk2 is required for cell wall integrity signaling, adhesion, and full virulence of the human pathogen Aspergillus fumigatus. Int J Med Microbiol 300:496–502. doi:10.1016/j.ijmm.2010.03.001

    Article  CAS  PubMed  Google Scholar 

  • do Nascimento AM, Goldman MH, Goldman GH (2002) Molecular characterization of ABC transporter-encoding genes in Aspergillus nidulans. Genet Mol Res 1:337–349

    PubMed  Google Scholar 

  • Ellis M, Al-Ramadi B, Bernsen R, Kristensen J, Alizadeh H, Hedstrom U (2009) Prospective evaluation of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever. J Med Microbiol 58:606–615. doi:10.1099/jmm.0.006452-0

    Article  CAS  PubMed  Google Scholar 

  • Espinel-Ingroff A, Diekema DJ, Fothergill A, Johnson E, Pelaez T, Pfaller MA, Rinaldi MG, Canton E, Turnidge J (2010) Wild-type MIC distributions and epidemiological cutoff values for the triazoles and six Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). J Clin Microbiol 48:3251–3257. doi:10.1128/JCM.00536-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Espinel-Ingroff A, Aller AI, Canton E, Castañón-Olivares LR, Chowdhary A, Cordoba S, Cuenca-Estrella M, Fothergill A, Fuller J, Govender N, Hagen F, Illnait-Zaragozi MT, Johnson E, Kidd S, Lass-Flörl C, Lockhart SR, Martins MA, Meis JF, Melhem MS, Ostrosky-Zeichner L, Pelaez T, Pfaller MA, Schell WA, St-Germain G, Trilles L, Turnidge J (2012) Cryptococcus neoformans-Cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole. Antimicrob Agents Chemother 56:5898–5906. doi:10.1128/AAC.01115-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrari S, Sanguinetti M, De Bernardis F, Torelli R, Posteraro B, Vandeputte P, Sanglard D (2011) Loss of mitochondrial functions associated with azole resistance in Candida glabrata results in enhanced virulence in mice. Antimicrob Agents Chemother 55:1852–1860. doi:10.1128/AAC.01271-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Forche A, Abbey D, Pisithkul T, Weinzierl MA, Ringstrom T, Bruck D, Petersen K, Berman J (2011) Stress alters rates and types of loss of heterozygosity in Candida albicans. MBio 2:e00129-11. doi:10.1128/mBio.00129-11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fothergill AW, Sutton DA, McCarthy DI, Wiederhold NP (2014) Impact of new antifungal breakpoints on antifungal resistance in Candida species. J Clin Microbiol 52:994–997. doi:10.1128/JCM.03044-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallagher JC, Dodds Ashley ES, Drew RH, Perfect JR (2003) Antifungal pharmacotherapy for invasive mould infections. Expert Opin Pharmacother 4:147–164. doi:10.1517/14656566.4.2.147

    Article  CAS  PubMed  Google Scholar 

  • Gaur NA, Manoharlal R, Saini P, Prasad T, Mukhopadhyay G, Hoefer M, Morschhäuser J, Prasad R (2005) Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element. Biochem Biophys Res Commun 332:206–214. doi:10.1016/j.bbrc.2005.04.113

    Article  CAS  PubMed  Google Scholar 

  • Georgopapadakou NH, Walsh TJ (1996) Antifungal agents: chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother 40:279–291

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ghannoum MA, Rice LB (1999) Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev 12:501–517

    CAS  PubMed  PubMed Central  Google Scholar 

  • Godoy MC, Viswanathan C, Marchiori E, Truong MT, Benveniste MF, Rossi S, Marom EM (2012) The reversed halo sign: update and differential diagnosis. Br J Radiol 85:1226–1235. doi:10.1259/bjr/54532316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greene RE, Schlamm HT, Oestmann JW, Stark P, Durand C, Lortholary O, Wingard JR, Herbrecht R, Ribaud P, Patterson TF, Troke PF, Denning DW, Bennett JE, de Pauw BE, Rubin RH (2007) Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis 44:373–379. doi:10.1086/509917

    Article  PubMed  Google Scholar 

  • Groll AH, Piscitelli SC, Walsh TJ (1998) Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol 44:343–500

    Article  CAS  PubMed  Google Scholar 

  • Hiemenz JW, Walsh TJ (1996) Lipid formulations of amphotericin B: recent progress and future directions. Clin Infect Dis 22(Suppl 2):S133–S144. doi:10.1093/clinids/22.Supplement_2.S13

    Article  CAS  PubMed  Google Scholar 

  • Holz RW (1974) The effects of the polyene antibiotics nystatin and amphotericin B on thin lipid membranes. Ann N Y Acad Sci 235:469–479. doi:10.1111/j.1749-6632.1974.tb43284.x

    Article  CAS  PubMed  Google Scholar 

  • Hu W, Sillaots S, Lemieux S, Davison J, Kauffman S, Breton A, Linteau A, Xin C, Bowman J, Becker J, Jiang B, Roemer T (2007) Essential gene identification and drug target prioritization in Aspergillus fumigatus. PLoS Pathog 3, e24. doi:10.1371/journal.ppat.0030024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Johnson G, Ferrini A, Dolan SK, Nolan T, Agrawal S, Doyle S, Bustin SA (2014) Biomarkers for invasive aspergillosis: the challenges continue. Biomark Med 8:429–451. doi:10.2217/bmm.13.129

    Article  CAS  PubMed  Google Scholar 

  • Kam AP, Xu J (2002) Diversity of commensal yeasts within and among healthy hosts. Diagn Microbiol Infect Dis 43:19–28. doi:10.1016/S0732-8893(02)00364-4

    Article  CAS  PubMed  Google Scholar 

  • Karnani N, Gaur NA, Jha S, Puri N, Krishnamurthy S, Goswami SK, Mukhopadhyay G, Prasad R (2004) SRE1 and SRE2 are two specific steroid-responsive modules of Candida drug resistance gene 1 (CDR1) promoter. Yeast 21:219–239. doi:10.1002/yea.1067

    Article  CAS  PubMed  Google Scholar 

  • Kelly SL, Lamb DC, Loeffler J, Einsele H, Kelly DE (1999) The G464S amino acid substitution in Candida albicans sterol 14alpha-demethylase causes fluconazole resistance in the clinic through reduced affinity. Biochem Biophys Res Commun 262:174–179. doi:10.1006/bbrc.1999.1136

    Article  CAS  PubMed  Google Scholar 

  • Kerridge D (1980) The plasma membrane of Candida albicans and its role in the action of antifungal drugs. In: Gooday GW, Lloyd D, Trinci APJ (eds) The eukaryotic microbial cell. Cambridge University Press, Cambridge, 103 p

    Google Scholar 

  • Kerridge D (1985) The protoplast membrane and antifungal drugs. In: Peberdy JF, Ferenczy L (eds) Fungal protoplasts: applications in biochemistry and genetics. Marcel Dekker Inc., New York, NY, 135 p

    Google Scholar 

  • Kim SY, Ko YJ, Jung KW, Strain A, Nielsen K, Bahn YS (2011) Hrk1 plays both Hog1-dependent and -independent roles in controlling stress response and antifungal drug resistance in Cryptococcus neoformans. PLoS One 6, e18769. doi:10.1371/journal.pone.0018769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ko YJ, Yu YM, Kim GB, Lee GW, Maeng PJ, Kim S, Floyd A, Heitman J, Bahn YS (2009) Remodeling of global transcription patterns of Cryptococcus neoformans genes mediated by the stress-activated HOG signaling pathways. Eukaryot Cell 8:1197–1217. doi:10.1128/EC.00120-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krcmery V, Barnes AJ (2002) Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J Hosp Infect 50:243–260. doi:10.1053/jhin.2001.1151

    Article  CAS  PubMed  Google Scholar 

  • Kullberg BJ, Arendrup MC (2015) Invasive Candidiasis. N Engl J Med 373:1445–1456. doi:10.1056/NEJMra1315399

    Article  CAS  PubMed  Google Scholar 

  • Kwon-Chung KJ, Chang YC (2012) Aneuploidy and drug resistance in pathogenic fungi. PLoS Pathog 8, e1003022. doi:10.1371/journal.ppat.1003022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon-Chung KJ, Rhodes JC (1986) Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans. Infect Immun 51:218–223

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lamping E, Baret PV, Holmes AR, Monk BC, Goffeau A, Cannon RD (2010) Fungal PDR transporters: phylogeny, topology, motifs and function. Fungal Genet Biol 47:127–142. doi:10.1016/j.fgb.2009.10.007

    Article  CAS  PubMed  Google Scholar 

  • Latge JP (1999) Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12:310–350

    CAS  PubMed  PubMed Central  Google Scholar 

  • MacPherson S, Akache B, Weber S, De Deken X, Raymond M, Turcotte B (2005) Candida albicans zinc cluster protein Upc2p confers resistance to antifungal drugs and is an activator of ergosterol biosynthetic genes. Antimicrob Agents Chemother 49:1745–1752. doi:10.1128/AAC.49.5.1745-1752.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, Ray SM, Thompson DL, Wilson LE, Fridkin SK (2014) Multistate point-prevalence survey of health care-associated infections. N Engl J Med 370:1198–1208. doi:10.1056/NEJMoa1306801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mansfield BE, Oltean HN, Oliver BG, Hoot SJ, Leyde SE, Hedstrom L, White TC (2010) Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi. PLoS Pathog 6, e1001126. doi:10.1371/journal.ppat.1001126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marichal P, Vanden Bossche H, Odds FC, Nobels G, Warnock DW, Timmerman V, Van Broeckhoven C, Fay S, Mose-Larsen P (1997) Molecular biological characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother 41:2229–2237

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez LR, Mihu MR, Han G, Frases S, Cordero RJ, Casadevall A, Friedman AJ, Friedman JM, Nosanchuk JD (2010) The use of chitosan to damage Cryptococcus neoformans biofilms. Biomaterials 31:669–679. doi:10.1016/j.biomaterials.2009.09.087

    Article  CAS  PubMed  Google Scholar 

  • McCormack FX, Whitsett JA (2002) The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest 109:707–712. doi:10.1172/jci15293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mellado E, Diaz-Guerra TM, Cuenca-Estrella M, Rodriguez-Tudela JL (2001) Identification of two different 14-alpha sterol demethylase related genes (cyp51A and cyp51B) in A. fumigatus and other A. species. J Clin Microbiol 39:2431–2438. doi:10.1128/JCM.39.7.2431-2438.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mellado E, Garcia-Effron G, Alcázar-Fuoli L, Melchers WJ, Verweij PE, Cuenca-Estrella M, Rodríguez-Tudela JL (2007) A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob Agents Chemother 51:1897–1904. doi:10.1128/AAC.01092-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messer SA, Moet GJ, Kirby JT, Jones RN (2009) Activity of contemporary antifungal agents, including the novel echinocandin anidulafungin, tested against Candida spp., Cryptococcus spp., and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2006 to 2007). J Clin Microbiol 47:1942–1946. doi:10.1128/JCM.02434-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer V (2008) A small protein that fights fungi: AFP as a new promising antifungal agent of biotechnological value. Appl Microbiol Biotechnol 78:17–28

    Article  CAS  PubMed  Google Scholar 

  • Mikulska M, Novelli A, Aversa F, Cesaro S, de Rosa FG, Girmenia C, Micozzi A, Sanguinetti M, Viscoli C (2012) Voriconazole in clinical practice. J Chemother 24:311–327. doi:10.1179/1973947812Y.0000000051

    Article  CAS  PubMed  Google Scholar 

  • Musher B, Fredricks D, Leisenring W, Balajee SA, Smith C, Marr KA (2004) Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid. J Clin Microbiol 42:5517–5522. doi:10.1128/jcm.42.12.5517-5522.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nanjappa SG, Klein BS (2014) Vaccine immunity against fungal infections. Curr Opin Immunol 28:27–33. doi:10.1016/j.coi.2014.01.014

    Article  CAS  PubMed  Google Scholar 

  • Nascimento AM, Goldman GH, Park S, Marras SA, Delmas G, Oza U, Lolans K, Dudley MN, Mann PA, Perlin DS (2003) Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob Agents Chemother 47:1719–1726. doi:10.1128/AAC.47.5.1719-1726.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Netea MG, Sutmuller R, Hermann C, van der Graaf CA, van der Meer JW, van Krieken JH, Hartung T, Adema G, Kullberg BJ (2004) Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J Immunol (Baltimore, Md: 1950) 172:3712–3718. doi:10.4049/jimmunol.172.6.3712

    Article  CAS  Google Scholar 

  • Nucci F, Nouer SA, Capone D, Anaissie E, Nucci M (2015) Fusariosis. Semin Respir Crit Care Med 36:706–714. doi:10.1055/s-0035-1562897

    Article  PubMed  Google Scholar 

  • Nunes AP, Schuenck RP, Bastos CC, Magnanini MM, Long JB, Iorio NL, Santos KR (2007) Heterogeneous resistance to vancomycin and teicoplanin among Staphylococcus spp. isolated from bacteremia. Braz J Infect Dis 11:345–350. doi:10.1590/S1413-86702007000300009

    Article  CAS  PubMed  Google Scholar 

  • Odds FC, Brown AJ, Gow NA (2003) Antifungal agents: mechanisms of action. Trends Microbiol 11:272–279. doi:10.1016/S0966-842X(03)00117-3

    Article  CAS  PubMed  Google Scholar 

  • Orsi CF, Bettua C, Pini P, Venturelli C, La Regina A, Morace G, Luppi M, Forghieri F, Bigliardi S, Luppi F, Codeluppi M, Girardis M, Blasi E (2015) Detection of Pneumocystis jirovecii and Aspergillus spp. DNA in bronchoalveolar lavage fluids by commercial real-time PCR assays:comparison with conventional diagnostic tests. New Microbiol 38:75–84

    PubMed  Google Scholar 

  • Panackal AA, Imhof A, Hanley EW, Marr KA (2006) Aspergillus ustus infections among transplant recipients. Emerg Infect Dis 12:403–408. doi:10.3201/eid1205.050670

    Article  PubMed  PubMed Central  Google Scholar 

  • Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of America (2009a) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535. doi:10.1086/596757

    Article  CAS  PubMed  Google Scholar 

  • Pappas PG, Chetchotisakd P, Larsen RA, Manosuthi W, Morris MI, Anekthananon T, Sungkanuparph S, Supparatpinyo K, Nolen TL, Zimmer LO, Kendrick AS, Johnson P, Sobel JD, Filler SG (2009b) A phase II randomized trial of amphotericin B alone or combined with fluconazole in the treatment of HIV-associated cryptococcal meningitis. Clin Infect Dis 48:1775–1783. doi:10.1086/599112

    Article  CAS  PubMed  Google Scholar 

  • Parks LW, Casey WM (1996) Fungal sterols. In: Prasad R, Ghannoum MA (eds) Lipids of pathogenic fungi. CRC Press, Boca Raton, FL, pp 63–82

    Google Scholar 

  • Pfaller MA, Diekema DJ, Ghannoum MA, Rex JH, Alexander BD, Andes D, Brown SD, Chaturvedi V, Espinel-Ingroff A, Fowler CL, Johnson EM, Knapp CC, Motyl MR, Ostrosky-Zeichner L, Sheehan DJ, Walsh TJ, Clinical and Laboratory Standards Institute Antifungal Testing Subcommittee (2009) Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods. J Clin Microbiol 47:3142–3146. doi:10.1128/JCM.00940-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pihet M, Vandeputte P, Tronchin G, Renier G, Saulnier P, Georgeault S, Mallet R, Chabasse D, Symoens F, Bouchara JP (2009) Melanin is an essential component for the integrity of the cell wall of Aspergillus fumigatus conidia. BMC Microbiol 9:177. doi:10.1186/1471-2180-9-177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pinjon E, Moran GP, Jackson CJ, Kelly SL, Sanglard D, Coleman DC, Sullivan DJ (2003) Molecular mechanisms of itraconazole resistance in Candida dubliniensis. Antimicrob Agents Chemother 47:2424–2437. doi:10.1128/AAC.47.8.2424-2437.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinjon E, Jackson CJ, Kelly SL, Sanglard D, Moran G, Coleman DC, Sullivan DJ (2005) Reduced azole susceptibility in genotype 3 Candida dubliniensis isolates associated with increased CdCDR1 and CdCDR2 expression. Antimicrob Agents Chemother 49:1312–1318. doi:10.1128/AAC.49.4.1312-1318.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Polonelli L, Casadevall A, Han Y, Bernardis F, Kirkland TN, Matthews RC, Adriani D, Boccanera M, Burnie JP, Cassone A, Conti S, Cutler JE, Frazzi R, Gregory C, Hodgetts S, Illidge C, Magliani W, Rigg G, Santoni G (2000) The efficacy of acquired humoral and cellular immunity in the prevention and therapy of experimental fungal infections. Med Mycol 38:281–292

    Article  PubMed  Google Scholar 

  • Rajendran R, Mowat E, McCulloch E, Lappin DF, Jones B, Lang S, Majithiya JB, Warn P, Williams C, Ramage G (2011) Azole resistance of Aspergillus fumigatus biofilms is partly associated with efflux pump activity. Antimicrob Agents Chemother 55:2092–2097. doi:10.1128/AAC.01189-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rex JH, Pfaller MA, Galgiani JN, Bartlett MS, Espinel-Ingroff A, Ghannoum MA, Lancaster M, Odds FC, Rinaldi MG, Walsh TJ, Barry AL (1997) Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards. Clin Infect Dis 24:235–247. doi:10.1093/clinids/24.2.235

    Article  CAS  PubMed  Google Scholar 

  • Riggle P, Kumamoto CA (2006) Transcriptional regulation of MDR1, encoding a drug efflux determinant, in fluconazole-resistant Candida albicans strains through an Mcm1p binding site. Eukaryot Cell 5:1957–1968. doi:10.1128/EC.00243-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodero L, Mellado E, Rodriguez AC, Salve A, Guelfand L, Cahn P, Rodriguez-Tudela JL (2003) G484S amino acid substitution in lanosterol 14-α demethylase (ERG11) is related to fluconazole resistance in a recurrent Cryptococcus neoformans clinical isolate. Antimicrob Agents Chemother 47:3653–3656. doi:10.1128/AAC.47.11.3653-3656.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez-Tudela JL, Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Monzon A, Cuenca-Estrella M (2008) Epidemiological cutoffs and cross-resistance to azole drugs in Aspergillus fumigatus. Antimicrob Agents Chemother 52:2468–2472. doi:10.1128/AAC.00156-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, Tandia F, Linteau A, Sillaots S, Marta C, Martel N, Veronneau S, Lemieux S, Kauffman S, Becker J, Storms R, Boone C, Bussey H (2003) Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol 50:167–181. doi:10.1046/j.1365-2958.2003.03697.x

    Article  CAS  PubMed  Google Scholar 

  • Rognon B, Kozovska Z, Coste AT, Pardini G, Sanglard D (2006) Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance. Microbiology 152:3701–3722. doi:10.1099/mic.0.29277-0

    Article  CAS  PubMed  Google Scholar 

  • Romani L (2004) Immunity to fungal infections. Nat Rev Immunol 4:1–23. doi:10.1038/nri1255

    Article  PubMed  CAS  Google Scholar 

  • Samaranayake YH, Cheung BP, Wang Y, Yau JY, Yeung KW, Samaranayake LP (2013) Fluconazole resistance in Candida glabrata is associated with increased bud formation and metallothionein production. J Med Microbiol 62:303–318. doi:10.1099/jmm.0.044123-0

    Article  CAS  PubMed  Google Scholar 

  • Samson RA, Visagie CM, Houbraken J, Hong SB, Hubka V, Klaassen CH, Perrone G, Seifert KA, Susca A, Tanney JB, Varga J, Kocsubé S, Szigeti G, Yaguchi T, Frisvad JC (2014) Phylogeny, identification and nomenclature of the genus Aspergillus. Stud Mycol 78:141–173. doi:10.1016/j.simyco.2014.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanglard D, Ischer F, Koymans L, Bille J (1998) Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrob Agents Chemother 42:241–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanguinetti M, Posteraro B, La Sorda M, Torelli R, Fiori B, Santangelo R, Delogu G, Fadda G (2006) Role of AFR1, an ABC transporter-encoding gene, in the in vivo response to fluconazole and virulence of Cryptococcus neoformans. Infect Immun 74:1352–1359. doi:10.1128/IAI.74.2.1352-1359.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanguinetti M, Posteraro B, Lass-Flörl C (2015) Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses 58(Suppl 2):2–13. doi:10.1111/myc.12330

    Article  PubMed  Google Scholar 

  • Saxena P, Shen SH, Morrissey O, Gooi JH (2015) Challenges in the management of invasive pulmonary zygomycosis: the Alfred experience. ANZ J Surg 85:700–701. doi:10.1111/ans.13264

    Article  PubMed  Google Scholar 

  • Seed PC (2014) The human mycobiome. Cold Spring Harb Perspect Med 5:a019810. doi:10.1101/cshperspect.a019810

    Article  PubMed  Google Scholar 

  • Selmecki A, Forche A, Berman J (2006) Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313:367–370. doi:10.1126/science.1128242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selmecki A, Gerami-Nejad M, Paulson C, Forche A, Berman J (2008) An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. Mol Microbiol 68:624–641. doi:10.1111/j.1365-2958.2008.06176.x

    Article  CAS  PubMed  Google Scholar 

  • Selmecki A, Forche A, Berman J (2010) Genomic plasticity of the human fungal pathogen Candida albicans. Eukaryot Cell 9:991–1008. doi:10.1128/EC.00060-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Semighini CP, Marins M, Goldman MH, Goldman GH (2002) Quantitative analysis of the relative transcript levels of ABC transporter Atr genes in Aspergillus nidulans by real-time reverse transcription-PCR assay. Appl Environ Microbiol 68:1351–1357. doi:10.1128/AEM.68.3.1351-1357.2002

    Article  CAS  PubMed  Google Scholar 

  • Shingu-Vazquez M, Traven A (2011) Mitochondria and fungal pathogenesis: drug tolerance, virulence, and potential for antifungal therapy. Eukaryot Cell 10:1376–1383. doi:10.1128/EC.05184-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva AP, Miranda IM, Guida A, Synnott J, Rocha R, Silva R, Amorim A, Pina-Vaz C, Butler G, Rodrigues AG (2011) Transcriptional profiling of azole resistant Candida parapsilosis strains. Antimicrob Agents Chemother 55:3546–3556. doi:10.1128/AAC.01127-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh A, Prasad R (2011) Comparative lipidomics of azole sensitive and resistant clinical isolates of Candida albicans reveals unexpected diversity in molecular lipid imprints. PLoS One 6:e19266. doi:10.1371/journal.pone.0019266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh A, Yadav V, Prasad R (2012) Comparative lipidomics in clinical isolates of Candida albicans reveal crosstalk between mitochondria, cell wall integrity and azole resistance. PLoS One 7:e39812. doi:10.1371/journal.pone.0039812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sionov E, Chang YC, Garraffo HM, Kwon-Chung KJ (2009) Heteroresistance tofluconazole in Cryptococcus neoformans is intrinsic and associated with virulence. Antimicrob Agents Chemother 53:2804–2815. doi:10.1128/AAC.00295-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sionov E, Lee H, Chang YC, Kwon-Chung KJ (2010) Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLoS Pathog 6, e1000848. doi:10.1371/journal.ppat.1000848

    Article  PubMed  PubMed Central  CAS  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 36:199–206. doi:10.1016/S1087-1845(02)00016-6

    Article  CAS  PubMed  Google Scholar 

  • Sloan DJ, Parris V (2014) Cryptococcal meningitis: epidemiology and therapeutic options. Clin Epidemiol 6:169–182. doi:10.2147/CLEP.S38850

    Article  PubMed  PubMed Central  Google Scholar 

  • Snelders E, van der Lee HA, Kuijpers J, Rijs AJ, Varga J, Samson RA, Mellado E, Donders AR, Melchers WJ, Verweij PE (2008) Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med 5, e219. doi:10.1371/journal.pmed.0050219

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Snelders E, Karawajczyk A, Schaftenaar G, Verweij PE, Melchers WJ (2010) Azole resistance profile of amino acid changes in A. fumigates cyp51A based on protein homology modeling. Antimicrob Agents Chemother 54:2425–2430. doi:10.1128/AAC.01599-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Speed B, Dunt D (1995) Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis 21:28–34. doi:10.1093/clinids/21.1.28

    Article  CAS  PubMed  Google Scholar 

  • Thursky KA, Playford EG, Seymour JF, Sorrell TC, Ellis DH, Guy SD, Gilroy N, Chu J, Shaw DR (2008) Recommendations for the treatment of established fungal infections. Intern Med J 38:496–520. doi:10.1111/j.1445-5994.2008.01725.x

    Article  CAS  PubMed  Google Scholar 

  • Torelli R, Posteraro B, Ferrari S, La Sorda M, Fadda G, Sanglard D, Sanguinetti M (2008) The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1-dependent azole resistance of Candida glabrata. Mol Microbiol 68:186–201. doi:10.1111/j.1365-2958.2008.06143.x

    Article  CAS  PubMed  Google Scholar 

  • Tsai HF, Sammons LR, Zhang X, Suffis SD, Su Q, Myers TG, Marr KA, Bennett JE (2010) Microarray and molecular analyses of the azole resistance mechanism in Candida glabrata oropharyngeal isolates. Antimicrob Agents Chemother 54:3308–3317. doi:10.1128/AAC.00535-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van der Meer JW, van de Veerdonk FL, Joosten LA, Kullberg BJ, Netea MG (2010) Severe Candida spp. infections: new insights into natural immunity. Int J Antimicrob Agents 36:S58–S62. doi:10.1016/j.ijantimicag.2010.11.013

    Article  PubMed  CAS  Google Scholar 

  • Vandeputte P, Larcher G, Bergès T, Renier G, Chabasse D, Bouchara JP (2005) Mechanisms of azole resistance in a clinical isolate of Candida tropicalis. Antimicrob Agents Chemother 49:4608–4615. doi:10.1128/AAC.49.11.4608-4615.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vandeputte P, Ferrari S, Coste AT (2012) Antifungal resistance and new strategies to control fungal infections. Int J Microbiol 713687. doi:10.1155/2012/713687

  • Vasicek EM, Berkow EL, Bruno VM, Mitchell AP, Wiederhold NP, Barker KS, Rogers PD (2014) Disruption of the transcriptional regulator Cas5 results in enhanced killing of Candida albicans by Fluconazole. Antimicrob Agents Chemother 58:6807–6818. doi:10.1128/AAC.00064-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Verweij PE, Mellado E, Melchers WJ (2007) Multiple-triazole-resistant aspergillosis. N Engl J Med 356:1481–1483. doi:10.1056/NEJMc061720

    Article  CAS  PubMed  Google Scholar 

  • Walsh TJ, Roilides E, Cortez K, Kottilil S, Bailey J, Lyman CA (2005) Control, immunoregulation, and expression of innate pulmonary host defenses against Aspergillus fumigatus. Med Mycol 43:S165–S172. doi:10.1080/13693780500064672

    Article  CAS  PubMed  Google Scholar 

  • Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF (2008) Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46:327–360. doi:10.1086/525258

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Wu J (2008) Antifungal activity of 25-azalanosterol against Candida species. Eur J Clin Microbiol Infect Dis 27:1131–1136. doi:10.1007/s10096-008-0554-y

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Zhang G, Zhang X, Wu S, Yin X, Zhang H (2012) Proteomic analysis of fluconazole resistance in Candida albicans. Afr J Pharm Pharmacol 6:1226–1230. doi:10.5897/AJPP11.801

    CAS  Google Scholar 

  • Wang B, Huang L-H, Zhao J-X, Wei M, Fang H, Wang D-Y, Wang H-F, Yin J-G, Xiang M (2015a) ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidiasis patients. Asian Pac J Trop Biomed 5:909–914. doi:10.1016/j.apjtb.2015.08.002

    Article  Google Scholar 

  • Wang Y, Liu JY, Shi C, Li WJ, Zhao Y, Yan L, Xiang MJ (2015b) Mutations in transcription factor Mrr2p contribute to fluconazole resistance in clinical isolates of Candida albicans. Int J Antimicrob Agents 46:552–559. doi:10.1016/j.ijantimicag.2015.08.001

    Article  CAS  PubMed  Google Scholar 

  • Warrilow AG, Melo N, Martel CM, Parker JE, Nes WD, Kelly SL, Kelly DE (2010) Expression, purification, and characterization of Aspergillus fumigatus sterol 14-alpha demethylase (CYP51) isoenzymes A and B. Antimicrob Agents Chemother 54:4225–4234. doi:10.1128/AAC.00316-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warris A, Weemaes CM, Verweij PE (2002) Multidrug resistance in Aspergillus fumigatus. N Engl J Med 347:2173–2174. doi:10.1056/NEJM200212263472618

    Article  PubMed  Google Scholar 

  • Willger SD, Puttikamonkul S, Kim KH, Burritt JB, Grahl N, Metzler LJ, Barbuch R, Bard M, Lawrence CB, Cramer RA Jr (2008) A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathog 4, e1000200. doi:10.1371/journal

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Won EJ, Shin JH, Choi MJ, Lee WG, Park YJ, Uh Y, Kim SY, Lee MK, Kim SH, Shin MG, Suh SP, Ryang DW (2015) Antifungal susceptibilities of bloodstream isolates of Candida species from nine hospitals in Korea: application of new antifungal breakpoints and relationship to antifungal usage. PLoS One 10, e0118770. doi:10.1371/journal.pone.0118770

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu CJ, Wang HC, Lee JC, Lo HJ, Dai CT, Chou PH, Ko WC, Chen YC (2015) Azole-resistant Aspergillus fumigatus isolates carrying TR34/L98H mutations in Taiwan. Mycoses 58:544–549. doi:10.1111/myc.12354

    Article  CAS  PubMed  Google Scholar 

  • Yapar N (2014) Epidemiology and risk factors for invasive candidiasis. Therap Clin Risk Manag 10:95–105. doi:10.2147/tcrm.s40160

    Article  Google Scholar 

  • Yoo JI, Choi CW, Kim HS, Yoo JS, Jeong YH, Lee YS (2012) Proteomic analysis of cellular and membrane proteins in fluconazole-resistant Candida glabrata. Osong Public Health Res Perspect 3:74–78. doi:10.1016/j.phrp.2012.04.001

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoo JI, Kim HS, Choi CW, Yoo JS, Yu JY, Lee YS (2013) Proteomic analysis of intracellular and membrane proteins from voriconazole-resistant Candida glabrata. Osong Public Health Res Perspect 4:293–300. doi:10.1016/j.phrp.2013.10.001

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Zhou S, Pan A, Li J, Liu B (2015) Surveillance of antifungal susceptibilities in clinical isolates of Candida species at 36 hospitals in China from 2009 to 2013. Int J Infect Dis 33:1–4. doi:10.1016/j.ijid.2014.12.033

    Article  PubMed  Google Scholar 

  • Zonios DI, Bennett JE (2008) Update on azole antifungals. Semin Respir Crit Care Med 29:198–210. doi:10.1055/s-2008-1063858

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Disease, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA

    Preetida J. Bhetariya

  2. Department of Biosciences, Jamia Milia Islamia University, New Delhi, 110025, India

    Neha Sharma

  3. Department of Biotechnology, Kumaun University, Nainital, Bhimtal Campus, Bhimtal, 263136, India

    Pragati Singh & Santosh K. Upadhyay

  4. Tumor Biology Group, National Institute of Pathology (NIOP), Indian Council of Medical Research (ICMR), 4909, Safdarjung Hospital Campus, New Delhi, 110029, India

    Priyanka Tripathi & Poonam Gautam PhD

Authors
  1. Preetida J. Bhetariya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neha Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pragati Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Priyanka Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Santosh K. Upadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Poonam Gautam PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Poonam Gautam PhD .

Editor information

Editors and Affiliations

  1. CSIR - Institute of Genomics and Integrative Biology, Delhi, India

    Gunjan Arora

  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Andaleeb Sajid

  3. CSIR - Institute of Genomics and Integrative Biology, Delhi, India

    Vipin Chandra Kalia

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bhetariya, P.J., Sharma, N., Singh, P., Tripathi, P., Upadhyay, S.K., Gautam, P. (2017). Human Fungal Pathogens and Drug Resistance Against Azole Drugs. In: Arora, G., Sajid, A., Kalia, V. (eds) Drug Resistance in Bacteria, Fungi, Malaria, and Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-48683-3_18

Download citation

Publish with us

Policies and ethics

Search

Navigation