Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters

Sanglard, D; Kuchler, K; Ischer, F; Pagani, J L; Monod, M; Bille, J

doi:10.1128/aac.39.11.2378

Cited by 815Antifungal resistance and susceptibilityDrug Transport and Resistance MechanismsFungal and yeast genetics research

Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters

Open access

Sanglard, D, Kuchler, K, Ischer, F, Pagani, J L, Monod, M, Bille, J·1995·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.39.11.2378PMC PMC162951

Open this paper in CoChat — free account

Abstract

Azole antifungal agents, and especially fluconazole, have been used widely to treat oropharyngeal candidiasis in patients with AIDS. An increasing number of cases of clinical resistance against fluconazole, often correlating with in vitro resistance, have been reported. To investigate the mechanisms of resistance toward azole antifungal agents at the molecular level in clinical C. albicans isolates, we focused on resistance mechanisms related to the cellular target of azoles, i.e., cytochrome P450(14DM) (14DM) and those regulating the transport or accumulation of fluconazole. The analysis of sequential isogenic C. albicans isolates with increasing levels of resistance to fluconazole from five AIDS patients showed that overexpression of the gene encoding 14DM either by gene amplification or by gene deregulation was not the major cause of resistance among these clinical isolates. We found, however, that fluconazole-resistant C. albicans isolates failed to accumulate 3H-labelled fluconazole. This phenomenon was reversed in resistant cells by inhibiting the cellular energy supply with azide, suggesting that resistance could be mediated by energy-requiring efflux pumps such as those described as ATP-binding cassette (ABC) multidrug transporters. In fact, some but not all fluconazole-resistant clinical C. albicans isolates exhibited up to a 10-fold relative increase in mRNA levels for a recently cloned ABC transporter gene called CDR1. In an azole-resistant C. albicans isolate not overexpressing CDR1, the gene for another efflux pump named BENr was massively overexpressed. This gene was cloned from C. albicans for conferring benomyl resistance in Saccharomyces cerevisiae. Therefore, at least the overexpression or the deregulation of these two genes potentially mediates resistance to azoles in C. albicans clinical isolates from AIDS patients with oropharyngeal candidiasis. Involvement of ABC transporters in azole resistance was further evidenced with S. cerevisiae mutants lacking specific multidrug transporters which were rendered hypersusceptible to azole derivatives including fluconazole, itraconazole, and ketoconazole.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1128/aac.39.11.2378

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Overexpression of the efflux transporter genes CDR1, CDR2, and MDR1 is a common mechanism of drug resistance in C. albicans.
“Overexpression of the efflux transporter genes CDR1 , CDR2 , and MDR1 is a common mechanism of drug resistance in this organism (10, 17, 26).”
From Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans (2012) · cites this paper as [26]
The Results and Discussion report increased CDR1 mRNA in some azole-resistant C. albicans isolates and implicate transporter overexpression in resistance. The paper examines CDR1 and BENr, not CDR2 or MDR1, and its findings in isolates from five AIDS patients do not establish that overexpression of all three named genes is a common resistance mechanism. (LLM, conf=0.88)
Experimental — accuracy not yet measured
In C. albicans, upregulation of ABC transporters Cdr1 and Cdr2 and major facilitator transporter Mdr1 have been implicated in azole resistance.
“For C. albicans, upregulation of the ATP-binding cassette (ABC) transporters, Cdr1 and Cdr2 (Candida drug resistance 1 and 2), and major facilitator transporter Mdr1 (multidrug resistance 1) have been implicated in azole resistance50,51.”
From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [50]
In two separate studies, isolates of C. albicans taken from HIV-infected individuals had increased mRNA levels of CDR1, which has been shown to confer resistance to the azole antifungals.
“In two separate studies, it was found that isolates of C. albicans taken from HIV-infected individuals had increased mRNA levels of CDR1, which has been shown to confer resistance to the azole antifungals.77–79”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans (2020) · cites this paper as [77]
ABC transporters Cdr1 and Cdr2 have both been well documented as drivers of azole resistance and were first implicated in clinical azole resistance in isolates in HIV-infected patients with oropharyngeal candidiasis.
“The ATP-binding cassette (ABC) transporters Cdr1 and Cdr2 have both been well documented as drivers of azole resistance and were first implicated in clinical azole resistance in isolates in HIV-infected patients with oropharyngeal candidiasis.75–77”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans (2020) · cites this paper as [77]
Overexpression of the ABC transporters Cdr1 and Cdr2 results in efflux of all azole antifungals in Candida albicans.
“Overexpression of the ATP binding cassette (ABC) transporters Cdr1 and Cdr2 results in the efflux of all azole antifungals”
From Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis (2015) · cites this paper as [12]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity
Feinberg, A. P., & Vogelstein, B. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90418-9 · Cited by 24,512 · see citing works
National Committee for Clinical Laboratory Standards
Bruck, E. (1980) · PEDIATRICS · doi:10.1542/peds.65.1.187 · Cited by 14,736 · see citing works
BIOCHEMISTRY OF MULTIDRUG RESISTANCE MEDIATED BY THE MULTIDRUG TRANSPORTER
Gottesman, M. M., & PASTAN, I. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.002125 · Cited by 3,515 · see citing works
Improved method for high efficiency transformation of intact yeast cells.
Gietz, D., Jean, A. S., Woods, R. A., & Schiestl, R. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.6.1425 · Cited by 3,379 · see citing works
Prevention of Drug Access to Bacterial Targets: Permeability Barriers and Active Efflux
Nikaido, H. (1994) · Science · doi:10.1126/science.8153625 · Cited by 1,542 · see citing works
Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematics
Selander, R. K., Caugant, D. A., Ochman, H., Musser, J. M., Gilmour, M. N., & Whittam, T. S. (1986) · Applied and Environmental Microbiology · doi:10.1128/aem.51.5.873-884.1986 · Cited by 1,379 · see citing works
Resistance of Candida species to fluconazole
Rex, J. H., Rinaldi, M. G., & Pfaller, M. A. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.1.1 · Cited by 879 · see citing works
Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals
Prasad, R., De Wergifosse, P., Goffeau, A., & Balzi, E. (1995) · Current Genetics · doi:10.1007/bf00352101 · Cited by 486 · see citing works
Azole antifungal agents: Emphasis on new triazoles
Saag, M. S., & Dismukes, W. E. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.1.1 · Cited by 474 · see citing works
PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1.
Balzi, E., Wang, M., Leterme, S., Van Dyck, L., & Goffeau, A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42155-7 · Cited by 447 · see citing works
Applications of high efficiency lithium acetate transformation of intact yeast cells using single‐stranded nucleic acids as carrier
Gietz, R. D., & Schiestl, R. H. (1991) · Yeast · doi:10.1002/yea.320070307 · Cited by 441 · see citing works
Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans
Hube, B., Monod, M., Schofield, D. A., Brown, A. J. P., & Gow, N. A. R. (1994) · Molecular Microbiology · doi:10.1111/j.1365-2958.1994.tb01269.x · Cited by 373 · see citing works
Self-citation
[11] Expression of genes in yeast using the ADCI promoter
Ammerer, G. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)01014-9 · Cited by 299 · see citing works
Resistance of Candida albicans to fluconazole during treatment of oropharyngeal candidiasis in a patient with AIDS: documentation by in vitro susceptibility testing and DNA subtype analysis
Redding, S., Smith, J., Farinacci, G., Rinaldi, M., Fothergill, A., Rhine-Chalberg, J., & Pfaller, M. (1994) · Clinical Infectious Diseases · doi:10.1093/clinids/18.2.240 · Cited by 269 · see citing works
Molecular mechanisms of drug resistance in fungi
BOSSCHE, H. V., Marichal, P., & Odds, F. C. (1994) · Trends in Microbiology · doi:10.1016/0966-842x(94)90618-1 · Cited by 255 · see citing works
Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection
Ruhnke, M., Eigler, A., Tennagen, I., Geiseler, B., Engelmann, E., & Trautmann, M. (1994) · Journal of Clinical Microbiology · doi:10.1128/jcm.32.9.2092-2098.1994 · Cited by 250 · see citing works
Fluconazole resistance in Candida glabrata
Hitchcock, C. A., Pye, G. W., Troke, P. F., Johnson, E. M., & Warnock, D. W. (1993) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.37.9.1962 · Cited by 244 · see citing works
Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene product. A yeast ABC transporter conferring mycotoxin resistance.
Bissinger, P. H., & Kuchler, K. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41760-1 · Cited by 234 · see citing works
Self-citation
Resistance of yeasts to azole-derivative antifungals
Odds, F. C. (1993) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/31.4.463 · Cited by 219 · see citing works
Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate
Fling, M. E., Kopf, J., Tamarkin, A., Gorman, J. A., Smith, H. A., & Koltin, Y. (1991) · Molecular and General Genetics MGG · doi:10.1007/bf00259685 · Cited by 205 · see citing works
Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype
Millon, L., Manteaux, A., Reboux, G., Drobacheff, C., Monod, M., Barale, T., & Michel-Briand, Y. (1994) · Journal of Clinical Microbiology · doi:10.1128/jcm.32.4.1115-1118.1994 · Cited by 205 · see citing works
Self-citation
Gene SNQ2 of Saccharomyces cerevislae, which confers resistance to 4-nitroquinoline-N-oxide and other chemicals, encodes a 169 kDa protein homologous to ATP-dependent permeases
Servos, J., Haase, E., & Brendel, M. (1993) · Molecular and General Genetics MGG · doi:10.1007/bf00277115 · Cited by 203 · see citing works
Characterization of an azole-resistant Candida glabrata isolate
BOSSCHE, H. V., Marichal, P., Odds, F. C., Jeune, L. L., & Coene, M. C. (1992) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.36.12.2602 · Cited by 203 · see citing works
Azole resistance inCandida albicans
Ryley, J. F., Wilson, R., & Barrett-Bee, K. J. (1984) · Medical Mycology · doi:10.1080/00362178485380091 · Cited by 182 · see citing works
Evaluation of a novel colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates
Pfaller, M. A., & Barry, A. L. (1994) · Journal of Clinical Microbiology · doi:10.1128/jcm.32.8.1992-1996.1994 · Cited by 160 · see citing works
Genetics and biochemistry of yeast multidrug resistance
Balzi, E., & Goffeau, A. (1994) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(94)90102-3 · Cited by 152 · see citing works
Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding cassette (ABC) superfamily, is required for multidrug resistance
Hirata, D., Yano, K., Miyahara, K., & Miyakawa, T. (1994) · Current Genetics · doi:10.1007/bf00310491 · Cited by 150 · see citing works
Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene
Ben-Yaacov, R., Knoller, S., Caldwell, G. A., Becker, J. M., & Koltin, Y. (1994) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.38.4.648 · Cited by 144 · see citing works
Telomeric and dispersed repeat sequences in Candida yeasts and their use in strain identification
Sadhu, C., McEachern, M. J., Rustchenko, E. P., Schmid, J., Soll, D. R., & Hicks, J. B. (1991) · Journal of Bacteriology · doi:10.1128/jb.173.2.842-850.1991 · Cited by 127 · see citing works
Development of autonomously replicating plasmids for Candida albicans.
Kurtz, M., Cortelyou, M. W., Miller, S. M., et al. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.1.209 · Cited by 120 · see citing works
Rapid detection and identification of Candida albicans and Torulopsis (Candida) glabrata in clinical specimens by species-specific nested PCR amplification of a cytochrome P-450 lanosterol-alpha-demethylase (L1A1) gene fragment
Burgener-Kairuz, P., Zuber, J. P., Jaunin, P., Buchman, T. G., Billé, J., & Rossier, M. (1994) · Journal of Clinical Microbiology · doi:10.1128/jcm.32.8.1902-1907.1994 · Cited by 114 · see citing works
Mutation in cytochrome P-450-dependent 14α-demethylase results in decreased affinity for azole antifungals
BOSSCHE, H. V., Marichal, P., Gorrens, J., Bellens, D., Moereels, H., & Janssen, P. A. J. (1990) · Biochemical Society Transactions · doi:10.1042/bst0180056 · Cited by 114 · see citing works
Fungal infections of the immunocompromised host: clinical and laboratory aspects
Musial, C. E., Cockerill, F. R., & Roberts, G. D. (1988) · Clinical Microbiology Reviews · doi:10.1128/cmr.1.4.349 · Cited by 104 · see citing works
The Lipid Composition of Azole-sensitive and Azole-resistant Strains of Candida albicans
Hitchcock, C. A., Barrett-Bee, K. J., & Russell, N. J. (1986) · Microbiology · doi:10.1099/00221287-132-9-2421 · Cited by 98 · see citing works
Correlation between in vitro susceptibility ofCandida albicans and fluconazole-resistant oropharyngeal candidiasis in HIV-infected patients
Troillet, N., Durussel, C., Billé, J., Glauser, M. P., & Chave, J. P. (1993) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/bf01992164 · Cited by 96 · see citing works
The lipid composition and permeability to azole of an azole- and polyene-resistant mutant ofCandida albicans
Hitchcock, C. A., Barrett-Bee, K. J., & Russell, N. J. (1987) · Medical Mycology · doi:10.1080/02681218780000041 · Cited by 80 · see citing works
Cloning and characterization of a yeast cytochrome b5-encoding gene which suppresses ketoconazole hypersensitivity in a NADPH-P-450 reductase-deficient strain
Truan, G., Epinat, J.-C., Rougeulle, C., Cullin, C., & Pompon, D. (1994) · Gene · doi:10.1016/0378-1119(94)90366-2 · Cited by 77 · see citing works
Epidemiology of Candida Infections in Aids
Odds, F. C., Schmid, J., & Soll, D. R. (1990) · Springer eBooks · doi:10.1007/978-1-4613-0655-9_5 · Cited by 61 · see citing works
DNA Subtypes and Fluconazole Susceptibilities of Candida albicans Isolates from the Oral Cavities of Patients with AIDS
Barchiesi, F., Hollis, R. J., McGough, D. A., Scalise, G., Rinaldi, M. G., & Pfaller, M. A. (1995) · Clinical Infectious Diseases · doi:10.1093/clinids/20.3.634 · Cited by 57 · see citing works
Isolation and analysis of ketoconazole resistant mutants ofSaccharomyces cerevisiae
Watson, P. F., Rose, M. E., & Kelly, S. L. (1988) · Medical Mycology · doi:10.1080/02681218880000231 · Cited by 45 · see citing works
A comparison of the sterol content of multiple isolates of the Candida albicans Darlington strain with other clinically azole-sensitive and -resistant strains
Howell, S. A., Mallet, A. I., & Noble, W. C. (1990) · Journal of Applied Bacteriology · doi:10.1111/j.1365-2672.1990.tb01564.x · Cited by 45 · see citing works
Correlation between antifungal susceptibility testing ofCandida isolates from patients with HIV infection and clinical results after treatment with fluconazole
Ruhnke, M., Eigler, A., Geiseler, B., et al. (1994) · Infection · doi:10.1007/bf01739024 · Cited by 44 · see citing works
Sterols inCandida AlbicansMutants Resistant to Polyene or Azole Antifungals, and of a Double MutantC. ALBICANS6.4
Hitchcock, C. A., Russell, N. J., & Barrett-Bee, K. J. (1987) · CRC Critical Reviews in Microbiology · doi:10.3109/10408418709104454 · Cited by 31 · see citing works
The Lipid Composition and Permeability to the Triazole Antifungal Antibiotic ICI 153066 of Serum-grown Mycelial Cultures of Candida albicans
Hitchcock, C. A., Barrett-Bee, K. J., & Russell, N. J. (1989) · Microbiology · doi:10.1099/00221287-135-7-1949 · Cited by 24 · see citing works
Regulation of the gene encoding translation elongation factor 3 during growth and morphogenesis in Candida albicans
Swoboda, R., Bertram, G., Colthurst, D. R., et al. (1994) · Microbiology · doi:10.1099/00221287-140-10-2611 · Cited by 23 · see citing works
DNA transformations of Candida tropicalis with replicating and integrative vectors
Sanglard, D., & Fiechter, A. (1992) · Yeast · doi:10.1002/yea.320081209 · Cited by 17 · see citing works
Self-citation
ATPase kinetics for wild‐type Saccharomyces cerevisiae F1‐ATPase and F1‐ATPase with the β‐subunit Thr197→Ser mutation
Mueller, D. M., Indyk, V. M., & MCGILL, L. (1994) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1994.tb18950.x · Cited by 14 · see citing works
Epidemiology of AIDS and its Opportunistic Infections
Chandler, F. W. (1990) · Springer eBooks · doi:10.1007/978-1-4613-0655-9_1 · Cited by 4 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

[14]14. Hanahan, D. 1985. Techniques for transformation of E. coli , p. 109-135. In D. M. Glover (ed.), DNA cloning. A practical approach. IRL Press, Oxford.

Sorted by citations

Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance
White, T. C., Marr, K. A., & Bowden, R. A. (1998) · Clinical Microbiology Reviews · doi:10.1128/cmr.11.2.382 · Cited by 1,353 · see citing works
Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences
Sanglard, D., & Odds, F. C. (2002) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(02)00181-0 · Cited by 784 · see citing works
Self-citation
Mechanisms of Antifungal Drug Resistance
Cowen, L. E., Sanglard, D., Howard, S. J., Rogers, P. D., & Perlin, D. S. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019752 · Cited by 647 · see citing works
Self-citation
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
White, T. C. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.7.1482 · Cited by 612 · see citing works
Resistance to Antifungal Agents: Mechanisms and Clinical Impact
Kanafani, Z. A., & Perfect, J. R. (2008) · Clinical Infectious Diseases · doi:10.1086/524071 · Cited by 619 · see citing works
Efflux-Mediated Antifungal Drug Resistance
Cannon, R. D., Lamping, E., Holmes, A. R., Niimi, K., Baret, P. V., Keniya, M. V., Tanabe, K., Niimi, M., Goffeau, A., & Monk, B. C. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00051-08 · Cited by 608 · see citing works
Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene
Sanglard, D., Ischer, F., Monod, M., & Bille, J. (1997) · Microbiology · doi:10.1099/00221287-143-2-405 · Cited by 587 · see citing works
Self-citation
Regulatory circuitry governing fungal development, drug resistance, and disease.
Shapiro, R. S., Robbins, N., & Cowen, L. E. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00045-10 · Cited by 576 · see citing works
Antifungal drug resistance of pathogenic fungi
Kontoyiannis, D. P., & Lewis, R. E. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08162-x · Cited by 553 · see citing works
Mechanism of Fluconazole Resistance in Candida albicans Biofilms: Phase-Specific Role of Efflux Pumps and Membrane Sterols
Mukherjee, P. K., Chandra, J., Kuhn, D. M., & Ghannoum, M. A. (2003) · Infection and Immunity · doi:10.1128/iai.71.8.4333-4340.2003 · Cited by 511 · see citing works
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
Perea, S., López-Ribot, J. L., Kirkpatrick, W. R., McAtee, R. K., Santillán, R. A., Martı́nez, M., Calabrese, D., Sanglard, D., & Patterson, T. F. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.10.2676-2684.2001 · Cited by 470 · see citing works
Self-citation
Resistance Mechanisms in Clinical Isolates of Candida albicans
White, T. C., Holleman, S., Dy, F., Mirels, L. F., & Stevens, D. A. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.6.1704-1713.2002 · Cited by 461 · see citing works
Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis
Scorzoni, L., de Paula e Silva, A. C. A., Marcos, C. M., Assato, P. A., de Melo, W. C. M. A., de Oliveira, H. C., Costa-Orlandi, C. B., Mendes-Giannini, M. J. S., & Fusco-Almeida, A. M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00036 · Cited by 418 · see citing works
Mechanisms of Candida Biofilm Drug Resistance
Taff, H. T., Mitchell, K. F., Edward, J. A., & Andes, D. R. (2013) · Future Microbiology · doi:10.2217/fmb.13.101 · Cited by 422 · see citing works
TAC1 , Transcriptional Activator of CDR Genes, Is a New Transcription Factor Involved in the Regulation of Candida albicans ABC Transporters CDR1 and CDR2
Coste, A. T., Karababa, M., Ischer, F., Bille, J., & Sanglard, D. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.6.1639-1652.2004 · Cited by 407 · see citing works
Self-citation
Candida albicans Mutations in the Ergosterol Biosynthetic Pathway and Resistance to Several Antifungal Agents
Sanglard, D., Ischer, F., Parkinson, T., Falconer, D., & Bille, J. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.8.2404-2412.2003 · Cited by 398 · see citing works
Self-citation
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
Coste, A., Turner, V., Ischer, F., Morschhäuser, J., Forche, A., Selmecki, A., Berman, J., Bille, J., & Sanglard, D. (2006) · Genetics · doi:10.1534/genetics.105.054767 · Cited by 385 · see citing works
Self-citation
Antifungal drug resistance among Candida species: mechanisms and clinical impact
Sanguinetti, M., Posteraro, B., & Lass‐Flörl, C. (2015) · Mycoses · doi:10.1111/myc.12330 · Cited by 394 · see citing works
Contribution of mutations in the cytochrome P450 14α-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans
Marichal, P., Koymans, L., Willemsens, S., Bellens, D., Verhasselt, P., Luyten, W., Borgers, M., Ramaekers, F. C. S., Odds, F. C., & Vanden Bossche, H. (1999) · Microbiology · doi:10.1099/00221287-145-10-2701 · Cited by 382 · see citing works
Clinical pharmacology of systemic antifungal agents: A comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development
Groll, A. H., Piscitelli, S. C., & Walsh, T. J. (1998) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60129-5 · Cited by 377 · see citing works
Quantitation of Ergosterol Content: Novel Method for Determination of Fluconazole Susceptibility of Candida albicans
Arthington-Skaggs, B. A., Jradi, H., Desai, T., & Morrison, C. J. (1999) · Journal of Clinical Microbiology · doi:10.1128/jcm.37.10.3332-3337.1999 · Cited by 365 · see citing works
The Transcription Factor Mrr1p Controls Expression of the MDR1 Efflux Pump and Mediates Multidrug Resistance in Candida albicans
Morschhäuser, J., Barker, K. S., Liu, T. T., Blaß-Warmuth, J., Homayouni, R., & Rogers, P. D. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030164 · Cited by 355 · see citing works
Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence
Sanglard, D., Ischer, F., Marchetti, O., Entenza, J., & Bille, J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03495.x · Cited by 350 · see citing works
Self-citation
Resistance to fluconazole and cross‐resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Δ5,6‐desaturation
Kelly, S. L., Lamb, D. C., Kelly, D. E., Manning, N. J., Loeffler, J., Hebart, H., Schumacher, U., & Einsele, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01360-9 · Cited by 351 · see citing works
Acquisition of Aneuploidy Provides Increased Fitness during the Evolution of Antifungal Drug Resistance
Selmecki, A. M., Dulmage, K., Cowen, L. E., Anderson, J. B., & Berman, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000705 · Cited by 319 · see citing works
Multiple Molecular Mechanisms Contribute to a Stepwise Development of Fluconazole Resistance in Clinical Candida albicans Strains
Franz, R., Kelly, S. L., Lamb, D. C., Kelly, D. E., Ruhnke, M., & Morschhäuser, J. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.12.3065 · Cited by 339 · see citing works
The ATP Binding Cassette Transporter Gene CgCDR1 from Candida glabrata Is Involved in the Resistance of Clinical Isolates to Azole Antifungal Agents
Sanglard, D., Ischer, F., Calabrese, D., Majcherczyk, P. A., & Bille, J. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.11.2753 · Cited by 337 · see citing works
Self-citation
Endogenous Reactive Oxygen Species Is an Important Mediator of Miconazole Antifungal Effect
Kobayashi, D., Kondo, K., Uehara, N., Otokozawa, S., Tsuji, N., Yagihashi, A., & Watanabe, N. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.10.3113-3117.2002 · Cited by 338 · see citing works
An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1
Selmecki, A., Gerami‐Nejad, M., Paulson, C., Forche, A., & Berman, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06176.x · Cited by 325 · see citing works
Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: Time for harmonization of CLSI and EUCAST broth microdilution methods
Pfaller, M. A., Andes, D., Diekema, D. J., Espinel-Ingroff, A., & Sheehan, D. (2010) · Drug Resistance Updates · doi:10.1016/j.drup.2010.09.002 · Cited by 314 · see citing works
Genotypic Evolution of Azole Resistance Mechanisms in Sequential Candida albicans Isolates
Coste, A., Selmecki, A., Forche, A., Diogo, D., Bougnoux, M.-E., d'Enfert, C., Berman, J., & Sanglard, D. (2007) · Eukaryotic Cell · doi:10.1128/ec.00151-07 · Cited by 305 · see citing works
Self-citation
Regulation of multidrug resistance in pathogenic fungi
Morschhäuser, J. (2010) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2009.08.002 · Cited by 300 · see citing works
Molecular mechanisms governing antifungal drug resistance
Lee, Y., Robbins, N., & Cowen, L. E. (2023) · npj Antimicrobials and Resistance · doi:10.1038/s44259-023-00007-2 · Cited by 304 · see citing works
Mutations in the multi‐drug resistance regulator MRR1 , followed by loss of heterozygosity, are the main cause of MDR1 overexpression in fluconazole‐resistant Candida albicans strains
Dunkel, N., Blaß, J., Rogers, P. D., & Morschhäuser, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06309.x · Cited by 278 · see citing works
Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation
Sanglard, D., Coste, A., & Ferrari, S. (2009) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2009.00578.x · Cited by 285 · see citing works
Self-citation
Recent insights into Candida albicans biofilm resistance mechanisms
Mathé, L., & Van Dijck, P. (2013) · Current Genetics · doi:10.1007/s00294-013-0400-3 · Cited by 271 · see citing works
Potent Synergism of the Combination of Fluconazole and Cyclosporine in Candida albicans
Marchetti, O., Moreillon, P., Glauser, M. P., Bille, J., & Sanglard, D. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.9.2373-2381.2000 · Cited by 252 · see citing works
Self-citation
Genetic Basis ofCandidaBiofilm Resistance Due to Drug‐Sequestering Matrix Glucan
Nett, J. E., Sanchez, H., Cain, M. T., & Andes, D. R. (2010) · The Journal of Infectious Diseases · doi:10.1086/651200 · Cited by 250 · see citing works
Draft genome of a commonly misdiagnosed multidrug resistant pathogen Candida auris
Chatterjee, S., Alampalli, S. V., Nageshan, R. K., Chettiar, S. T., Joshi, S., & Tatu, U. S. (2015) · BMC Genomics · doi:10.1186/s12864-015-1863-z · Cited by 247 · see citing works
Role of ATP-Binding-Cassette Transporter Genes in High-Frequency Acquisition of Resistance to Azole Antifungals in Candida glabrata
Sanglard, D., Ischer, F., & Bille, J. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.4.1174-1183.2001 · Cited by 247 · see citing works
Self-citation
Gain-of-Function Mutations in UPC2 Are a Frequent Cause of ERG11 Upregulation in Azole-Resistant Clinical Isolates of Candida albicans
Flowers, S. A., Barker, K. S., Berkow, E. L., Toner, G., Chadwick, S. G., Gygax, S. E., Morschhäuser, J., & Rogers, P. D. (2012) · Eukaryotic Cell · doi:10.1128/ec.00215-12 · Cited by 239 · see citing works
“Overexpression of the efflux transporter genes CDR1, CDR2, and MDR1 is a common mechanism of drug resistance in this organism (10, 17, 26).”
Background
A Gain-of-Function Mutation in the Transcription Factor Upc2p Causes Upregulation of Ergosterol Biosynthesis Genes and Increased Fluconazole Resistance in a Clinical Candida albicans Isolate
Dunkel, N., Liu, T. T., Barker, K. S., Homayouni, R., Morschhäuser, J., & Rogers, P. D. (2008) · Eukaryotic Cell · doi:10.1128/ec.00103-08 · Cited by 236 · see citing works
CRZ1 , a target of the calcineurin pathway in Candida albicans
Karababa, M., Valentino, E., Pardini, G., Coste, A. T., Bille, J., & Sanglard, D. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.05037.x · Cited by 231 · see citing works
Self-citation
Review on Antifungal Resistance Mechanisms in the Emerging Pathogen Candida auris
Chaabane, F., Graf, A., Jequier, L., & Coste, A. T. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02788 · Cited by 223 · see citing works
Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients
Phillips, P., Shafran, S., Garber, G., Rotstein, C., Smaill, F., Fong, I., Salit, I., Miller, M., Williams, K., Conly, J. M., et al. (1997) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/bf01726360 · Cited by 221 · see citing works
Upregulation of ERG Genes in Candida Species by Azoles and Other Sterol Biosynthesis Inhibitors
Henry, K. W., Nickels, J. T., & Edlind, T. D. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.10.2693-2700.2000 · Cited by 216 · see citing works
Mechanism of Fluconazole Resistance in Candida krusei
Orozco, A. S., Higginbotham, L. M., Hitchcock, C. A., Parkinson, T., Falconer, D., Ibrahim, A. S., Ghannoum, M. A., & Filler, S. G. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.10.2645 · Cited by 218 · see citing works
Mechanism of Increased Fluconazole Resistance in Candida glabrata during Prophylaxis
Bennett, J. E., Izumikawa, K., & Marr, K. A. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.5.1773-1777.2004 · Cited by 217 · see citing works
Molecular biological characterization of an azole-resistant Candida glabrata isolate
Marichal, P., Vanden Bossche, H., Odds, F. C., Nobels, G., Warnock, D. W., Timmerman, V, Van Broeckhoven, C., Fay, S., & Mose-Larsen, P. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.10.2229 · Cited by 210 · see citing works
Evolution of Drug Resistance in Experimental Populations of Candida albicans
Cowen, L. E., Sanglard, D., Calabrese, D., Sirjusingh, C., Anderson, J. B., & Kohn, L. M. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.6.1515-1522.2000 · Cited by 207 · see citing works
Self-citation
Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate
Slaven, J. W., Anderson, M. J., Sanglard, D., Dixon, G. K., Bille, J., Roberts, I. S., & Denning, D. W. (2002) · Fungal Genetics and Biology · doi:10.1016/s1087-1845(02)00016-6 · Cited by 202 · see citing works
Self-citation
Identification and Expression of Multidrug Transporters Responsible for Fluconazole Resistance in Candida dubliniensis
Moran, G. P., Sanglard, D., Donnelly, S. M., Shanley, D. B., Sullivan, D. J., & Coleman, D. C. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.7.1819 · Cited by 197 · see citing works
Self-citation
Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes
Schwarzmüller, T., Ma, B., Hiller, E., Istel, F., Tscherner, M., Brunke, S., Ames, L., Firon, A., Green, B., Cabral, V., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004211 · Cited by 191 · see citing works
Self-citation
Heteroresistance to Fluconazole in Cryptococcus neoformans Is Intrinsic and Associated with Virulence
Sionov, E., Chang, Y. C., Garraffo, H. M., & Kwon-Chung, K. J. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00295-09 · Cited by 179 · see citing works
Identification and Characterization of Four Azole-Resistant erg3 Mutants of Candida albicans
Martel, C. M., Parker, J. E., Bader, O., Weig, M., Gross, U., Warrilow, A. G. S., Rolley, N., Kelly, D. E., & Kelly, S. L. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00348-10 · Cited by 168 · see citing works
A Clinical Isolate of Candida albicans with Mutations in ERG11 (Encoding Sterol 14α-Demethylase) and ERG5 (Encoding C22 Desaturase) Is Cross Resistant to Azoles and Amphotericin B
Martel, C. M., Parker, J. E., Bader, O., Weig, M., Gross, U., Warrilow, A. G. S., Kelly, D. E., & Kelly, S. L. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00303-10 · Cited by 165 · see citing works
Rapid, Transient Fluconazole Resistance in Candida albicans Is Associated with Increased mRNA Levels of CDR
Marr, K. A., Lyons, C. N., Rustad, T., Bowden, R. A., & White, T. C. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.10.2584 · Cited by 166 · see citing works
Interface of Candida albicans Biofilm Matrix-Associated Drug Resistance and Cell Wall Integrity Regulation
Nett, J. E., Sanchez, H., Cain, M. T., Ross, K. M., & Andes, D. R. (2011) · Eukaryotic Cell · doi:10.1128/ec.05126-11 · Cited by 168 · see citing works
Functional Genomic Analysis of Fluconazole Susceptibility in the Pathogenic Yeast Candida glabrata : Roles of Calcium Signaling and Mitochondria
Kaur, R., Castaño, I., & Cormack, B. P. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.5.1600-1613.2004 · Cited by 167 · see citing works
Rhodamine 6G efflux for the detection of CDR1-overexpressing azole-resistant Candidaalbicans strains
Maesaki, S., Marichal, P., Bossche, H. V., Sanglard, D., & Kohno, S. (1999) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/44.1.27 · Cited by 162 · see citing works
Self-citation
Targeting Efflux Pumps to Overcome Antifungal Drug Resistance
Holmes, A. R., Cardno, T. S., Strouse, J. J., Ivnitski-Steele, I., Keniya, M. V., Lackovic, K., Monk, B. C., Sklar, L. A., & Cannon, R. D. (2016) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0050 · Cited by 156 · see citing works
Experimental Induction of Fluconazole Resistance in Candida tropicalis ATCC 750
Barchiesi, F., Calabrese, D., Sanglard, D., Falconi Di Francesco, L., Caselli, F., Giannini, D., Giacometti, A., Gavaudan, S., & Scalise, G. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.6.1578-1584.2000 · Cited by 145 · see citing works
Self-citation
Quantitation of Candida albicans Ergosterol Content Improves the Correlation between In Vitro Antifungal Susceptibility Test Results and In Vivo Outcome after Fluconazole Treatment in a Murine Model of Invasive Candidiasis
Arthington-Skaggs, B. A., Warnock, D. W., & Morrison, C. J. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.8.2081-2085.2000 · Cited by 142 · see citing works
The ATP‐binding cassette transporter–encoding gene CgSNQ2 is contributing to the CgPDR1‐dependent azole resistance of Candida glabrata
Torelli, R., Posteraro, B., Ferrari, S., La Sorda, M., Fadda, G., Sanglard, D., & Sanguinetti, M. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06143.x · Cited by 141 · see citing works
Self-citation
Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter‐encoding gene, CnAFR1, involved in the resistance to fluconazole
Posteraro, B., Sanguinetti, M., Sanglard, D., La Sorda, M., Boccia, S., Romano, L., Morace, G., & Fadda, G. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03281.x · Cited by 143 · see citing works
Self-citation
Multidrug resistance in fungi: regulation of transporter-encoding gene expression
Paul, S., & Moye-Rowley, W. S. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00143 · Cited by 137 · see citing works
Functional Characterization of Candida albicans ABC Transporter Cdr1p
Shukla, S., Saini, P., Smriti, Jha, S., Ambudkar, S. V., & Prasad, R. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.6.1361-1375.2003 · Cited by 135 · see citing works
Molecular Mechanisms of Drug Resistance in Clinical Candida Species Isolated from Tunisian Hospitals
Eddouzi, J., Parker, J. E., Vale-Silva, L. A., Coste, A., Ischer, F., Kelly, S., Manai, M., & Sanglard, D. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00555-13 · Cited by 128 · see citing works
Self-citation
Clinical breakpoints for voriconazole and Candida spp. revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria
Pfaller, M. A., Andes, D., Arendrup, M. C., Diekema, D. J., Espinel-Ingroff, A., Alexander, B. D., Brown, S. D., Chaturvedi, V., Fowler, C. L., Ghannoum, M. A., et al. (2011) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2011.03.002 · Cited by 130 · see citing works
Relative Contributions of the Candida albicans ABC Transporters Cdr1p and Cdr2p to Clinical Azole Resistance
Tsao, S., Rahkhoodaee, F., & Raymond, M. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00926-08 · Cited by 126 · see citing works
The ABCs of Candida albicans multidrug transporter Cdr1
Prasad, R., Banerjee, A., Khandelwal, N. K., & Dhamgaye, S. (2015) · Eukaryotic Cell · doi:10.1128/ec.00137-15 · Cited by 123 · see citing works
Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae
Souza, A. C. R., Fuchs, B. B., Pinhati, H. M. S., Siqueira, R. A., Hagen, F., Meis, J. F., Mylonakis, E., & Colombo, A. L. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01177-15 · Cited by 121 · see citing works
Sequencing, Disruption, and Characterization of the Candida albicans Sterol Methyltransferase ( ERG6 ) Gene: Drug Susceptibility Studies in erg6 Mutants
Jensen-Pergakes, K. L., Kennedy, M. A., Lees, N. D., Barbuch, R., Koegel, C., & Bard, M. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.5.1160 · Cited by 121 · see citing works
The CRH Family Coding for Cell Wall Glycosylphosphatidylinositol Proteins with a Predicted Transglycosidase Domain Affects Cell Wall Organization and Virulence of Candida albicans
Pardini, G., De Groot, P. W. J., Coste, A. T., Karababa, M., Klis, F. M., de Koster, C. G., & Sanglard, D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606361200 · Cited by 121 · see citing works
Self-citation
The development of fluconazole resistance in Candida albicans – an example of microevolution of a fungal pathogen
Morschhäuser, J. (2016) · Journal of Microbiology · doi:10.1007/s12275-016-5628-4 · Cited by 118 · see citing works
Potent Synergistic Effect of Doxycycline with Fluconazole against Candida albicans Is Mediated by Interference with Iron Homeostasis
Fiori, A., & Van Dijck, P. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06017-11 · Cited by 112 · see citing works
The ATP‐binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae: a novel target for the transcription factors Pdr1 and Pdr3
Mahé, Y., Parle‐McDermott, A., Nourani, A., Delahodde, A., Lamprecht, A., & Kuchler, K. (1996) · Molecular Microbiology · doi:10.1111/j.1365-2958.1996.tb02493.x · Cited by 117 · see citing works
Self-citation
Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans
Marchetti, O., Entenza, J. M., Sanglard, D., Bille, J., Glauser, M. P., & Moreillon, P. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.11.2932-2938.2000 · Cited by 113 · see citing works
Self-citation
Azole Drugs Are Imported By Facilitated Diffusion in Candida albicans and Other Pathogenic Fungi
Mansfield, B. E., Oltean, H. N., Oliver, B. G., Hoot, S. J., Leyde, S. E., Hedstrom, L., & White, T. C. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001126 · Cited by 111 · see citing works
Stable azole drug resistance associated with a substrain of Candida albicans from an HIV‐infected patient
White, T., Pfaller, M., Rinaldi, M., Smith, J., & Redding, S. (1997) · Oral Diseases · doi:10.1111/j.1601-0825.1997.tb00336.x · Cited by 107 · see citing works
Formation of Azole-Resistant Candida albicans by Mutation of Sterol 14-Demethylase P450
Asai, K., Tsuchimori, N., Okonogi, K., Perfect, J. R., Gotoh, O., & Yoshida, Y. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.5.1163 · Cited by 102 · see citing works
Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungusCandida albicans
Nishimoto, A. T., Sharma, C., & Rogers, P. D. (2020) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkz400 · Cited by 102 · see citing works
Isolation of a Putative Candida albicans Transcriptional Regulator Involved in Pleiotropic Drug Resistance by Functional Complementation of a pdr1 pdr3 Mutation in Saccharomyces cerevisiae
Talibi, D., & Raymond, M. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.1.231-240.1999 · Cited by 101 · see citing works
Genetic Dissection of Azole Resistance Mechanisms in Candida albicans and Their Validation in a Mouse Model of Disseminated Infection
MacCallum, D. M., Coste, A., Ischer, F., Jacobsen, M. D., Odds, F. C., & Sanglard, D. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01645-09 · Cited by 98 · see citing works
Self-citation
Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis
Berkow, E. L., Manigaba, K., Parker, J. E., Barker, K. S., Kelly, S. L., & Rogers, P. D. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01358-15 · Cited by 95 · see citing works
The role of the cell wall in fungal pathogenesis
Arana, D. M., Prieto, D., Román, E., Nombela, C., Alonso‐Monge, R., & Pla, J. (2009) · Microbial Biotechnology · doi:10.1111/j.1751-7915.2008.00070.x · Cited by 92 · see citing works
Activation of the Multiple Drug Resistance Gene MDR1 in Fluconazole-Resistant, Clinical Candida albicans Strains Is Caused by Mutations in a trans -Regulatory Factor
Wirsching, S., Michel, S., Köhler, G., & Morschhäuser, J. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.2.400-404.2000 · Cited by 88 · see citing works
Azole Resistance in Candida glabrata
Whaley, S. G., & Rogers, P. D. (2016) · Current Infectious Disease Reports · doi:10.1007/s11908-016-0554-5 · Cited by 85 · see citing works
Multiple Patterns of Resistance to Fluconazole in Candida glabrata Isolates from a Patient with Oropharyngeal Candidiasis Receiving Head and Neck Radiation
Redding, S. W., Kirkpatrick, W. R., Saville, S., Coco, B. J., White, W., Fothergill, A., Rinaldi, M., Eng, T., Patterson, T. F., & Lopez-Ribot, J. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.2.619-622.2003 · Cited by 85 · see citing works
Novel ERG11 and TAC1b Mutations Associated with Azole Resistance in Candida auris
Li, J., Coste, A. T., Liechti, M., Bachmann, D., Sanglard, D., & Lamoth, F. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02663-20 · Cited by 82 · see citing works
Self-citation
Antifungal drug resistance in Candida species
Morace, G., Perdoni, F., & Borghi, E. (2014) · Journal of Global Antimicrobial Resistance · doi:10.1016/j.jgar.2014.09.002 · Cited by 80 · see citing works
diskImageR: quantification of resistance and tolerance to antimicrobial drugs using disk diffusion assays
Gerstein, A. C., Rosenberg, A., Hecht, I., & Berman, J. (2016) · Microbiology · doi:10.1099/mic.0.000295 · Cited by 63 · see citing works
Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance
Rognon, B., Kozovska, Z., Coste, A. T., Pardini, G., & Sanglard, D. (2006) · Microbiology · doi:10.1099/mic.0.29277-0 · Cited by 71 · see citing works
Self-citation
Calcineurin Signaling and Membrane Lipid Homeostasis Regulates Iron Mediated MultiDrug Resistance Mechanisms in Candida albicans
Hameed, S., Dhamgaye, S., Singh, A., Goswami, S. K., & Prasad, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018684 · Cited by 69 · see citing works
Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance
Niimi, M., Niimi, K., Takano, Y., Holmes, A. R., Fischer, F. J., Uehara, Y., & Cannon, R. D. (2004) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkh456 · Cited by 69 · see citing works
Heterozygosity and functional allelic variation in theCandida albicansefflux pump genesCDR1andCDR2
Holmes, A. R., Tsao, S., Ong, S., Lamping, E., Niimi, K., Monk, B. C., Niimi, M., Kaneko, A., Holland, B. R., Schmid, J., et al. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05357.x · Cited by 68 · see citing works
Persistent Candida albicans colonization and molecular mechanisms of azole resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients
Siikala, E., Rautemaa, R., Richardson, M., Saxen, H., Bowyer, P., & Sanglard, D. (2010) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkq354 · Cited by 66 · see citing works
Self-citation
Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata
Brun, S., Aubry, C., Lima, O., Filmon, R., Bergès, T., Chabasse, D., & Bouchara, J.-P. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.3.847-853.2003 · Cited by 64 · see citing works
In-vitro resistance to azoles associated with mitochondrial DNA deficiency in Candida glabrata
DEFONTAINE, A., BOUCHARA, J.-P., DECLERK, P., PLANCHENAULT, C., CHABASSE, D., & HALLET, J.-N. (1999) · Journal of Medical Microbiology · doi:10.1099/00222615-48-7-663 · Cited by 65 · see citing works
Prevalence of Vaginal Colonization by Drug‐ResistantCandidaSpecies in College‐Age Women with Previous Exposure to Over‐the‐Counter Azole Antifungals
Mathema, B., Cross, E., Dun, E., Park, S., Bedell, J., Slade, B., Williams, M., Riley, L., Chaturvedi, V., & Perlin, D. S. (2001) · Clinical Infectious Diseases · doi:10.1086/322600 · Cited by 65 · see citing works

Cavitating pulmonary cryptococcosis developing in an HIV antibody patient despite prior treatment with fluconazole.
Coker, R. J., Bell, D., Peters, B. S., et al. (1992) · Sexually Transmitted Infections · doi:10.1136/sti.68.1.42 · Cited by 3 · see citing works
In Vitro Activities of Novel Azole Compounds ATTAF-1 and ATTAF-2 against Fluconazole-Susceptible and -Resistant Isolates of Candida Species
Fakhim, H., Emami, S., Vaezi, A., Hashemi, S. M., Faeli, L., Diba, K., Dannaoui, É., & Badali, H. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01106-16 · Cited by 29 · see citing works
A subdose of fluconazole alters the virulence ofCryptococcus gattiiduring murine cryptococcosis and modulates type I interferon expression
Fontes, A. C. L., de Oliveira, D. B., Santos, J. R. A., Carneiro, H. C. S., Ribeiro, N. D. Q., Oliveira, L. V. N., Barcellos, V. A., da Paixão, T. A., Abrahão, J. S., de Resende, M. A., et al. (2016) · Medical Mycology · doi:10.1093/mmy/myw056 · Cited by 7 · see citing works
Anti-Candida Activity of New Azole Derivatives Alone and in Combination with Fluconazole
Shi, C., Liu, C., Liu, J., Wang, Y., Li, J., & Xiang, M.-J. (2015) · Mycopathologia · doi:10.1007/s11046-015-9899-9 · Cited by 6 · see citing works
Action of fluconazole (UK-49, 858) in relation to other systemic antifungal azoles
Hughes, C. E., & Beggs, W. H. (1987) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/19.2.171 · Cited by 39 · see citing works

Authors: Sanglard, D., Kuchler, K., Ischer, F., Pagani, J. L., Monod, M., & Bille, J.
Affiliations: Centre Hospitalier Universitaire Vaudois (CH)
Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
ORCID: Sanglard, D
Kuchler, K
Pagani, J L
Monod, M
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 1995-11
Volume: 39
Issue: 11
Pages: 2378-2386
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.39.11.2378
PMC: PMC162951
OpenAlex: W2115130703
Cited by: 815
References: 48
Citations by year: 2026: 10 · 2025: 19 · 2024: 13 · 2023: 12 · 2022: 11 · 2021: 20 · 2020: 15 · 2019: 25 · 2018: 24 · 2017: 32 · 2016: 24 · 2015: 27 · 2014: 26 · 2013: 26 · 2012: 22
FWCI: 32.03
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Funders: Bundesamt für Gesundheit
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: Candida albicans, azole resistance, fluconazole resistance, multidrug transporter, ABC transporters, CDR1, efflux pumps, oropharyngeal candidiasis, AIDS patients, drug accumulation, gene overexpression, benomyl resistance
MeSH terms: Antifungal Agents, Azoles, Base Sequence, Candida albicans, Candidiasis, Oral, DNA, Fungal, Drug Resistance, Microbial, Fungal Proteins, Genes, Fungal, Humans, Microbial Sensitivity Tests, Molecular Sequence Data, Nucleic Acid Hybridization, Plasmids, RNA, Fungal, Saccharomyces cerevisiae, Blotting, Northern, Fluconazole, Polymerase Chain Reaction, AIDS-Related Opportunistic Infections, Drug Resistance, Multiple, ATP-Binding Cassette Transporters, ATP Binding Cassette Transporter, Subfamily B, Member 1, Membrane Transport Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks