CRS–MIS in C andida glabrata: sphingolipids modulate echinocandin–Fks interaction

Healey, Kelley R.; Katiyar, Santosh K.; Raj, Shriya; Edlind, Thomas D.

doi:10.1111/j.1365-2958.2012.08194.x

Cited by 79Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

CRS–MIS in C andida glabrata: sphingolipids modulate echinocandin–Fks interaction

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Healey, Kelley R., Katiyar, Santosh K., Raj, Shriya, Edlind, Thomas D.·2012·Molecular Microbiology

DOI 10.1111/j.1365-2958.2012.08194.xPMC PMC3472958

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Abstract

Infections with the azole-refractory yeast Candida glabrata are now commonly treated with the echinocandins caspofungin (CSF) or micafungin (MCF). True resistance (> 32-fold decreased susceptibility) to these lipopeptide inhibitors of cell wall synthesis is rare and strictly associated with mutations in integral membrane proteins Fks1 or Fks2. In contrast, mutants exhibiting 4- to 32-fold CSF reduced susceptibility (CRS) were readily selected in vitro, and surprisingly demonstrated 4- to 32-fold MCF increased susceptibility (MIS). Sequencing and gene deletion demonstrated that CRS-MIS is Fks-independent. To explore alternative mechanisms, we initially employed Saccharomyces cerevisiae, and observed that CRS was conferred by multiple mutations (fen1Δ, sur4Δ, cka2Δ and tsc10-ts) disrupting sphingolipid biosynthesis. Following this lead, C. glabrata fen1Δ and cka2Δ deletants were constructed, and shown to exhibit CRS-MIS. Sphingolipid analysis of CRS-MIS laboratory mutants and clinical isolates demonstrated elevated dihydrosphingosine (DHS) and phytosphingosine (PHS) levels, and consistent with this sequencing revealed fen1, sur4, ifa38 and sur2 mutations. Moreover, exogenous DHS or PHS conferred a CRS-MIS phenotype on wild-type C. glabrata. Exogenous PHS failed, however, to suppress CRS-MIS in a sur2 mutant blocked in conversion of DHS to PHS, implying that accumulation of these intermediates confers CRS-MIS. We conclude that membrane sphingolipids modulate echinocandin-Fks interaction.

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The drug specificity of caspofungin heteroresistance is partly rooted in differential interaction with the drug target within the altered membrane environment resulting from regulated sphingolipid metabolism.
“The drug specificity further underscores its unique mechanism, which is partly rooted in their differential interaction with the drug target within the altered membrane environment resulting from regulated sphingolipid metabolism [50]”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [50]
The Discussion proposes that altered membrane sphingolipids could weaken caspofungin’s interaction with Fks while strengthening micafungin’s. But it says the mechanism remains to be elucidated and explicitly calls this interaction a speculative model; the citing sentence presents it as an established basis for drug specificity. (LLM, conf=0.86)
Experimental — accuracy not yet measured
In C. glabrata, mutations or stress-induced alterations in sphingolipid biosynthesis can lead to paradoxically caspofungin-reduced-susceptibility but micafungin-increased-susceptibility.
“In C. glabrata, studies have demonstrated that mutations or stress‐induced alterations in sphingolipid biosynthesis can lead to paradoxically caspofungin‐reduced‐susceptibility but micafungin‐increased‐susceptibility, a form of drug‐specific susceptibility phenotype [50].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [50]
The Abstract and Discussion report that mutations affecting sphingolipid biosynthesis in C. glabrata produce reduced caspofungin susceptibility alongside increased micafungin susceptibility. The paper also reports that added sphingolipid intermediates reproduce the phenotype, but the passages do not establish that stress-induced alterations cause it. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Recent evidence suggests that membrane lipid composition, particularly sphingolipid biosynthesis, may contribute to drug-specific susceptibility profiles.
“recent evidence suggests that membrane lipid composition, particularly sphingolipid biosynthesis, may contribute to drug‐specific susceptibility profiles [50, 52, 53].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [50]
Mutations in FEN1 have been related to acquisition of resistance to echinocandins in C. glabrata, with some mutations leading to reduced susceptibility to caspofungin but not to micafungin.
“Mutations in the FEN1 gene have been related to acquisition of resistance to echinocandins in C. glabrata, with some mutations leading to reduced susceptibility to caspofungin but not to micafungin (Healey et al., 2012).”
From Genome Comparisons of Candida glabrata Serial Clinical Isolates Reveal Patterns of Genetic Variation in Infecting Clonal Populations (2019) · cites this paper as Healey et al., 2012

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A rapid boiling method for the preparation of bacterial plasmids
Holmes, D. S., & Quigley, M. E. (1981) · Analytical Biochemistry · doi:10.1016/0003-2697(81)90473-5 · Cited by 3,198 · see citing works
Clinical Practice Guidelines for the Management Candidiasis: 2009 Update by the Infectious Diseases Society of America
Pappas, P. G., Kauffman, C. A., Andes, D., Benjamin, D. K., Calandra, T. F., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B.-J., Zeichner, L. O., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/596757 · Cited by 3,191 · see citing works
Echinocandin antifungal drugs
Denning, D. W. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14472-8 · Cited by 1,131 · 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
Resistance to echinocandin-class antifungal drugs.
Perlin, D. S. (2007) · Drug Resistance Updates · doi:10.1016/j.drup.2007.04.002 · Cited by 512 · see citing works
ELO2 and ELO3, Homologues of theSaccharomyces cerevisiae ELO1 Gene, Function in Fatty Acid Elongation and Are Required for Sphingolipid Formation
Oh, C.-S., Toke, D. A., MANDALA, S. M., & Martin, C. E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.28.17376 · Cited by 487 · see citing works
Widespread aneuploidy revealed by DNA microarray expression profiling
Hughes, T. R., Roberts, C. J., Dai, H. A., Jones, A. R., Meyer, M. R., Slade, D., Burchard, J., Dow, S., Ward, T. R., Kidd, M. J., et al. (2000) · Nature Genetics · doi:10.1038/77116 · Cited by 482 · see citing works
The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-beta-D-glucan synthase.
Douglas, C. M., Foor, F., Marrinan, J. A., Morin, N., Nielsen, J. B., Dahl, A. M., Mazur, P., Baginsky, W., Li, W., & el-Sherbeini, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.26.12907 · Cited by 401 · see citing works
Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-D-glucan synthase inhibitors
Douglas, C. M., D'Ippolito, J. A., Shei, G.-J., Meinz, M., Onishi, J. C., Marrinan, J. A., Li, W., Abruzzo, G. K., Flattery, A. M., Bartizal, K. F., et al. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.11.2471 · Cited by 344 · see citing works
Effect of Candida glabrata FKS1 and FKS2 Mutations on Echinocandin Sensitivity and Kinetics of 1,3-β- <scp>d</scp> -Glucan Synthase: Implication for the Existing Susceptibility Breakpoint
Garcia-Effron, G., Lee, S., Park, S., Cleary, J. D., & Perlin, D. S. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00443-09 · Cited by 323 · see citing works
Fungal ß(1,3)-D-glucan synthesis
Douglas, C. M. (2001) · Medical Mycology · doi:10.1080/mmy.39.1.55.66 · Cited by 312 · see citing works
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
Cdc50p, a Protein Required for Polarized Growth, Associates with the Drs2p P-Type ATPase Implicated in Phospholipid Translocation inSaccharomyces cerevisiae
Saito, K., Fujimura‐Kamada, K., Furuta, N., Kato, U., Umeda, M., & Tanaka, K. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-11-0829 · Cited by 252 · see citing works
The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits of serine palmitoyltransferase, the initial enzyme in sphingolipid synthesis.
Nagiec, M. M., Baltisberger, J. A., Wells, G. B., Lester, R. L., & Dickson, R. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.17.7899 · Cited by 233 · see citing works
Pdr1 regulates multidrug resistance in Candida glabrata : gene disruption and genome‐wide expression studies
Vermitsky, J., Earhart, K. D., Smith, W. L., Homayouni, R., Edlind, T. D., & Rogers, P. D. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05235.x · Cited by 233 · see citing works
Self-citation
The Saccharomyces cerevisiae TSC10/YBR265w Gene Encoding 3-Ketosphinganine Reductase Is Identified in a Screen for Temperature-sensitive Suppressors of the Ca2+-sensitive csg2Δ Mutant
Beeler, T., Bačíková, D., Gable, K., Hopkins, L., Johnson, C. R., Slife, H., & Dunn, T. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.46.30688 · Cited by 202 · see citing works
Characterization and Gene Cloning of 1,3-beta-D-Glucan Synthase from Saccharomyces Cerevisiae
Inoue, S., Takewakt, N., Takasuka, T., Mio, T., Adachi, M., Fujii, Y., Miyamoto, C., Arisawa, M., Furuichi, Y., & Watanabe, T. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.0845d.x · Cited by 201 · see citing works
Breakthrough invasive candidiasis in patients on micafungin.
Pfeiffer, C. D., Garcia-Effron, G., Zaas, A. K., Perfect, J. R., Perlin, D. S., & Alexander, B. D. (2010) · Journal of Clinical Microbiology · doi:10.1128/jcm.02390-09 · Cited by 196 · see citing works
Candida albicans and Candida glabrata Clinical Isolates Exhibiting Reduced Echinocandin Susceptibility
Katiyar, S. K., Pfaller, M. A., & Edlind, T. D. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00349-06 · Cited by 189 · see citing works
Self-citation
Analysis of β-1,3-Glucan Assembly in Saccharomyces cerevisiae Using a Synthetic Interaction Network and Altered Sensitivity to Caspofungin
Lesage, G., Sdicu, A.-M., Ménard, P., Shapiro, J., Hussein, S., & Bussey, H. (2004) · Genetics · doi:10.1534/genetics.167.1.35 · Cited by 166 · see citing works
Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance.
Ben-Ami, R., Garcia-Effron, G., Lewis, R. E., Gamarra, S., Leventakos, K., Perlin, D. S., & Kontoyiannis, D. P. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir351 · Cited by 162 · see citing works
Wild-Type MIC Distributions and Epidemiological Cutoff Values for the Echinocandins and Candida spp
Pfaller, M. A., Boyken, L. B., Hollis, R. J., Kroeger, J. S., Messer, S. A., Tendolkar, S., Jones, R. N., Turnidge, J. D., & Diekema, D. J. (2009) · Journal of Clinical Microbiology · doi:10.1128/jcm.01590-09 · Cited by 154 · see citing works
Sphingolipid Analysis by High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS)
Bielawski, J., Pierce, J. S., Snider, J. M., Rembiesa, B. M., Szulc, Z. M., & Bielawska, A. E. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6741-1_3 · Cited by 146 · see citing works
FKS Mutations and Elevated Echinocandin MIC Values among Candida glabrata Isolates from U.S. Population-Based Surveillance
Zimbeck, A. J., Iqbal, N., Ahlquist, A. M., Farley, M. M., Harrison, L. H., Chiller, T., & Lockhart, S. R. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00836-10 · Cited by 136 · see citing works
Low Prevalence of fks1 Hot Spot 1 Mutations in a Worldwide Collection of Candida Strains
Castanheira, M., Woosley, L. N., Diekema, D. J., Messer, S. A., Jones, R. N., & Pfaller, M. A. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01711-09 · Cited by 125 · see citing works
Echinocandin inhibition of 1,3‐β‐D‐glucan synthase from Candida albicans
Sawistowska-Schröder, E. T., Kerridge, D., & Perry, H. (1984) · FEBS Letters · doi:10.1016/0014-5793(84)81032-7 · Cited by 123 · see citing works
Genomic Approach to Identification of Mutations Affecting Caspofungin Susceptibility in Saccharomyces cerevisiae
Markovich, S., Yekutiel, A., Shalit, I., Shadkchan, Y., & Osherov, N. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.10.3871-3876.2004 · Cited by 122 · see citing works
The isolation and characterization of a mutant strain of Saccharomyces cerevisiae that requires a long chain base for growth and for synthesis of phosphosphingolipids.
Wells, G. B., & Lester, R. L. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44439-5 · Cited by 119 · see citing works
Reduced Candida glabrata Susceptibility Secondary to an FKS1 Mutation Developed during Candidemia Treatment
Cleary, J. D., Garcia-Effron, G., Chapman, S. W., & Perlin, D. S. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01568-07 · Cited by 118 · see citing works
Serum Differentially Alters the Antifungal Properties of Echinocandin Drugs
Paderu, P., García‐Effrón, G., Balashov, S. V., Delmas, G., Park, S., & Perlin, D. S. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01536-06 · Cited by 109 · see citing works
Novel FKS Mutations Associated with Echinocandin Resistance in Candida Species
García‐Effrón, G., Chua, D. J., Tomada, J. R. T., DiPersio, J. R., Perlin, D. S., Ghannoum, M. A., & Bonilla, H. F. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00998-09 · Cited by 104 · see citing works
Roles for Sphingolipids in Saccharomyces cerevisiae
Dickson, R. C. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6741-1_15 · Cited by 103 · see citing works
Deacylation of echinocandin B by Actinoplanes utahensis.
BOECK, L. V. D., Fukuda, D. S., Abbott, B. J., et al. (1989) · The Journal of Antibiotics · doi:10.7164/antibiotics.42.382 · Cited by 89 · see citing works
Cilofungin (LY121019) inhibits Candida albicans (1-3)-beta-D-glucan synthase activity
Taft, C. S., Stark, T., & Selitrennikoff, C. P. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.12.1901 · Cited by 79 · see citing works
Topological and Mutational Analysis of Saccharomyces cerevisiae Fks1
Johnson, M. E., & Edlind, T. D. (2012) · Eukaryotic Cell · doi:10.1128/ec.00082-12 · Cited by 70 · see citing works
Self-citation
Update on Echinocandin Antifungals
Kauffman, C. A., & Carver, P. L. (2008) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-2008-1063859 · Cited by 69 · see citing works
Ceramide/Long-Chain Base Phosphate Rheostat in Saccharomyces cerevisiae : Regulation of Ceramide Synthesis by Elo3p and Cka2p
Kobayashi, S. D., & Nagiec, M. M. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.2.284-294.2003 · Cited by 65 · see citing works
Multiple Functional Domains of the Yeast l,3-β-Glucan Synthase Subunit Fks1p Revealed by Quantitative Phenotypic Analysis of Temperature-Sensitive Mutants
Okada, H., Abe, M., Minemura, M., Hirata, A., Qadota, H., Morishita, K., Ohnuki, S., Nogami, S., & Ohya, Y. (2010) · Genetics · doi:10.1534/genetics.109.109892 · Cited by 63 · see citing works
Use of Epidemiological Cutoff Values To Examine 9-Year Trends in Susceptibility of Candida Species to Anidulafungin, Caspofungin, and Micafungin
Pfaller, M. A., Boyken, L. B., Hollis, R. J., Kroeger, J. S., Messer, S. A., Tendolkar, S., & Diekema, D. J. (2010) · Journal of Clinical Microbiology · doi:10.1128/jcm.02120-10 · Cited by 59 · see citing works
Cloning and characterization of GNS1: a Saccharomyces cerevisiae gene involved in synthesis of 1,3-beta-glucan in vitro
El-Sherbeini, M., & Clemas, J. A. (1995) · Journal of Bacteriology · doi:10.1128/jb.177.11.3227-3234.1995 · Cited by 58 · see citing works
Promoter-dependent disruption of genes: simple, rapid, and specific PCR-based method with application to three different yeast
Edlind, T. D., Henry, K. W., Vermitsky, J., Edlind, M. P., Raj, S., & Katiyar, S. K. (2005) · Current Genetics · doi:10.1007/s00294-005-0008-3 · Cited by 38 · see citing works
Self-citation
General resistance to sterol biosynthesis inhibitors inSaccharomyces cerevisiae
Ladevèze, V., Marcireau, C., Delourme, D., & Karst, F. (1993) · Lipids · doi:10.1007/bf02537499 · Cited by 36 · see citing works
Photoaffinity Analog of the Semisynthetic Echinocandin LY303366: Identification of Echinocandin Targets in Candida albicans
Radding, J. A., Heidler, S. A., & Turner, W. W. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.5.1187 · Cited by 35 · see citing works
Candida glabrata Mutants Demonstrating Paradoxical Reduced Caspofungin Susceptibility but Increased Micafungin Susceptibility
Healey, K. R., Katiyar, S. K., Castanheira, M., Pfaller, M. A., & Edlind, T. D. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00044-11 · Cited by 30 · see citing works
Self-citation
The Echinocandin “Target” Identified by Cross-Linking Is a Homolog of Pil1 and Lsp1, Sphingolipid-Dependent Regulators of Cell Wall Integrity Signaling
Edlind, T. D., & Katiyar, S. K. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.11.4491.2004 · Cited by 22 · see citing works
Self-citation
Echinocandins: pharmacokinetic and therapeutic issues.
Cleary, J. D. (2009) · PubMed · Cited by 11 · see citing works

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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
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Husain, F., Yadav, A., Sah, S. K., Hayes, J. J., & Rustchenko, E. (2022) · Microorganisms · doi:10.3390/microorganisms11010023 · Cited by 10 · see citing works
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Li, Y., Hou, X., Li, R., Liao, K., Ma, L., Wang, X., Ji, P., Kong, H., Xia, Y., Ding, H., et al. (2023) · BMC Microbiology · doi:10.1186/s12866-023-03105-3 · Cited by 7 · see citing works
Tn-seq screens in Candida glabrata treated with echinocandins and ibrexafungerp reveal pathways of antifungal resistance and cross-resistance
Nickels, T. J., & Cunningham, K. W. (2025) · mSphere · doi:10.1128/msphere.00270-25 · Cited by 8 · see citing works
Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata
Su, Y., Li, Y., Xiao, M., Guo, D., Perlin, D. S., Shor, E., Xu, Y., & Li, Y. (2026) · Advanced Science · doi:10.1002/advs.76369 · Cited by 2 · see citing works

Relative Frequency of Paradoxical Growth and Trailing Effect with Caspofungin, Micafungin, Anidulafungin, and the Novel Echinocandin Rezafungin against Candida Species
Tóth, Z., Forgács, L., Kardos, T., Kovács, R., Locke, J. B., Kardos, G., Nagy, F., Borman, A. M., Adnan, A., & Majoros, L. (2020) · Journal of Fungi · doi:10.3390/jof6030136 · Cited by 20 · see citing works
Medical Claims and Current Applications of the Potent Echinocandin Antifungals
Smith, L., & Lu, S. (2009) · Recent Patents on Anti-Infective Drug Discovery · doi:10.2174/157489110790112563 · Cited by 2 · see citing works
Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis - review of the literature
Kofla, G., & Ruhnke, M. (2011) · European Journal of Medical Research · doi:10.1186/2047-783x-16-4-159 · Cited by 153 · see citing works
The role of caspofungin and the echinocandins in the antifungal armamentarium.
Morrison, V. A. (2002) · PubMed · Cited by 15 · see citing works
Echinocandin antifungals: review and update
Morrison, V. A. (2006) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.4.2.325 · Cited by 85 · see citing works

Authors: Healey, K. R., Katiyar, S. K., Raj, S., & Edlind, T. D.
Affiliations: Drexel University (US)
Department of Microbiology and Immunology Drexel University College of Medicine Philadelphia PA 19129 USA
Corresponding author: Edlind, Thomas D.
ORCID: Healey, Kelley R.
Raj, Shriya
Venue: Molecular Microbiology
Publisher: Wiley
Published: 2012-08-22
Volume: 86
Issue: 2
Pages: 303-313
ISSN: 0950-382X (ISSN-L)
1365-2958
DOI: 10.1111/j.1365-2958.2012.08194.x
PMC: PMC3472958
OpenAlex: W1576223091
Cited by: 79
References: 46
Citations by year: 2026: 5 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 3
FWCI: 3.98
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Molecular Microbiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Medical University of South Carolina
National Institutes of Health
National Institute of Allergy and Infectious Diseases (AI075272., R01AI075272)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords: Candida glabrata, echinocandin resistance, micafungin, caspofungin, sphingolipids, dihydrosphingosine, phytosphingosine, FKS1, FKS2, FEN1, SUR2, cell wall synthesis inhibitors, antifungal susceptibility, membrane lipid metabolism
MeSH terms: Caspofungin, Micafungin, Fungal Proteins, Membrane Proteins, Microbial Sensitivity Tests, Sphingolipids, Candida glabrata, Echinocandins, Lipopeptides

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CRS–MIS in C andida glabrata: sphingolipids modulate echinocandin–Fks interaction

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