The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Correlating Echinocandin MIC and Kinetic Inhibition of fks1 Mutant Glucan Synthases for Candida albicans : Implications for Interpretive Breakpoints
Open accessAbstract
ABSTRACT A detailed kinetic characterization of echinocandin inhibition was performed for mutant 1,3-β- d -glucan synthase enzymes from clinical isolates of Candida albicans with nine different FKS1 mutations resulting in high MICs. Among 14 mutant Fks1p enzymes studied, the kinetic parameters 50% inhibitory concentration and K i increased 50-fold to several thousandfold relative to those for the wild type. Enzymes with mutations at Ser645 (S645P, S645Y, and S645F) within hot spot 1 showed the most prominent decrease in sensitivity, while those with mutations at the N- and C-terminal ends of hot spot 1 generally retained greater sensitivity to all three drugs. Kinetic inhibitions by caspofungin, micafungin, and anidulafungin were comparable among the fks1 mutant enzymes, although absolute values did vary with specific mutations. Amino acid substitutions in Fks1p did not alter K m values, although some mutations decreased the V max . Given the association of FKS1 mutations with clinical resistance, an evaluation of the kinetic parameters for the inhibition of mutant 1,3-β- d -glucan synthase as a function of the MIC enabled an independent evaluation of the recently adopted susceptibility breakpoint for echinocandin drugs. Overall, a breakpoint MIC of ≥2 μg/ml for caspofungin captured nearly 100% of fks1 C. albicans strains when a kinetic inhibition rise threshold of ≤50-fold for the K i was used as a measure of susceptibility. A similar MIC breakpoint for micafungin and anidulafungin was less inclusive, and a projected MIC of ≥0.5 μg/ml was required for >95% coverage of clinical isolates. However, when MIC determinations were performed in the presence of 50% serum, all fks1 mutants showed MIC values of ≥2 μg/ml for the three echinocandin drugs. The 1,3-β- d -glucan synthase kinetic inhibition data support the proposed susceptibility breakpoint for caspofungin in C. albicans , but a lower susceptibility breakpoint (≤0.5 μg/ml) may be more appropriate for anidulafungin and micafungin. Overall, the data indicate that MIC testing with caspofungin may serve as a surrogate marker for resistance among the class of echinocandin drugs.
Overview
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
Cites
Statistics
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“Given that specific Fks amino acid substitutions that decrease sensitivity of the 1,3-β-D-glucan synthase enzyme to echinocandins also reduce the enzyme catalytic capacity, the Fks2 S663P mutation may confer a fitness cost in terms of reduced growth or viability in the absence of the drug [36], [39].”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [39]
In the citing paper
“Mutations in FKS1 did not alter substrate binding but lowered V max values [122].”
From Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents (2013) · cites this paper as [122]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
The determination of enzyme inhibitor constants
Dixon, M. (1953) · Biochemical Journal · doi:10.1042/bj0550170 · Cited by 4,066
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
Resistance to echinocandin-class antifungal drugs.
Perlin, D. S. (2007) · Drug Resistance Updates · doi:10.1016/j.drup.2007.04.002 · Cited by 512
Self-citationPerea, 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
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
Park, S., Kelly, R., Kahn, J. N., Robles, J., Hsu, M.-J., Register, E., Li, W., Vyas, V., Fan, H., Abruzzo, G., et al. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.8.3264-3273.2005 · Cited by 434
Self-citationPfaller, M. A., Boyken, L. B., Hollis, R. J., Kroeger, J. S., Messer, S. A., Tendolkar, S., & Diekema, D. J. (2007) · Journal of Clinical Microbiology · doi:10.1128/jcm.01901-07 · Cited by 391
Discovery of Novel Antifungal (1,3)-β- d -Glucan Synthase Inhibitors
Onishi, J. C., Meinz, M., Thompson, J. R., Curotto, J. E., Dreikorn, S., Rosenbach, M. J., Douglas, C. M., Abruzzo, G. K., Flattery, A. M., Kong, L., et al. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.2.368-377.2000 · Cited by 329
Garcia-Effron, G., Katiyar, S. K., Park, S., Edlind, T. D., & Perlin, D. S. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00262-08 · Cited by 323
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–258 of 258
Antifungal Activity of Morpholine and Piperidine Based Surfactants
Wieczorek, D., Kwaśniewska, D., Hsu, L.-H., Shen, T., & Chen, Y. (2020) · Tenside Surfactants Detergents · doi:10.3139/113.110667 · Cited by 6
The Role of Resistance in Candida Infections: Epidemiology and Treatment
Sobel, J. D., & Akins, R. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-47266-9_18 · Cited by 6
A benchmark dataset for validating FKS1 mutations in Candida auris
Misas, E., Parnell, L. A., Rajeev, M., López, L. F., dos Santos, A. R., Mudge, Z. B., Gade, L., Forsberg, K., Lyman, M., Sexton, D. J., et al. (2025) · Microbiology Spectrum · doi:10.1128/spectrum.03147-24 · Cited by 6
Ostroumova, O. S., & Efimova, S. S. (2023) · Antibiotics · doi:10.3390/antibiotics12121716 · Cited by 7
Yadav, A., Sah, S. K., Perlin, D. S., & Rustchenko, E. P. (2024) · Journal of Fungi · doi:10.3390/jof10030224 · Cited by 5
Self-citationThe Mechanisms of Resistance to Echinocandin Class of Antifungal Drugs
Niimi, K., & Niimi, M. (2009) · Nippon Ishinkin Gakkai Zasshi · doi:10.3314/jjmm.50.057 · Cited by 6
Emerging Resistance to Azoles and Echinocandins: Clinical Relevance and Laboratory Detection
Espinel‐Ingroff, A., Pfaller, M. A., Cantón, E., & Pemán, J. (2010) · Current Fungal Infection Reports · doi:10.1007/s12281-010-0026-6 · Cited by 5
Caspofungin-Non-Susceptible Candida orthopsilosis Isolated from Onychomycosis in Iran.
Mohammadi, R., Mirhendi, H., Hedayati, M. T., & Badali, H. (2017) · PubMed Central · Cited by 5
Zhang, M., Zhao, Y., Cui, H., Huang, W., Xiong, K., Yang, S., Duan, Y., He, Y., Yang, L., Su, C., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2417721122 · Cited by 4
Sah, S. K., Yadav, A., Kruppa, M., & Rustchenko, E. P. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.03295-23 · Cited by 5
Multidrug- and Cross-Resistant Candida: the Looming Threat
Lackner, M., Martín‐Vicente, A., & Lass‐Flörl, C. (2014) · Current Fungal Infection Reports · doi:10.1007/s12281-014-0210-1 · Cited by 4
Ahmadi, A., Mahmoudi, S., Rezaie, S., Hashemi, S. J., Dannaoui, É., Badali, H., Ghaffari, M., Aala, F., Izadi, A., Maleki, A., et al. (2019) · Journal of Global Antimicrobial Resistance · doi:10.1016/j.jgar.2019.11.003 · Cited by 5
Definitions and Epidemiology of Candida Species not Susceptible to Echinocandins
Pfaller, M. A., Diekema, D. J., Castanheira, M., & Jones, R. N. (2011) · Current Fungal Infection Reports · doi:10.1007/s12281-011-0053-y · Cited by 4
Dupont, B. (2010) · Journal de Mycologie Médicale · doi:10.1016/j.mycmed.2010.05.001 · Cited by 3
Zheng, L., Xu, Y., Wang, C., Yang, F. J., Dong, Y., & Guo, L. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.01790-23 · Cited by 3
Jones, R. N., Castanheira, M., & Pfaller, M. A. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00330-10 · Cited by 3
Advances in Antifungal Susceptibility Testing of Candida, 2010–2012
Pfaller, M. A., Castanheira, M., & Jones, R. N. (2012) · Current Fungal Infection Reports · doi:10.1007/s12281-012-0092-z · Cited by 3
Baxa, J. A. V. D. (2014) · Clinical Microbiology Open Access · doi:10.4172/2327-5073.1000154 · Cited by 2
Molecular Detection of Resistance to Echinocandins
Posteraro, B., Vella, A., Carolis, E. D., & Sanguinetti, M. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6515-1_23 · Cited by 3
Relevante Aspekte zu Candida-Spezies in der Dermatologie
Müller, V. L., Kreuter, A., Uhrlaß, S., & Nenoff, P. (2025) · Die Dermatologie · doi:10.1007/s00105-025-05538-5 · Cited by 3
Tonon, E., Cecchetto, R., Carrera, M., Sorrentino, A., Zeni, G., Turri, G., Mantoan, M., Palmisano, A., Lagni, A., Lotti, V., et al. (2025) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkaf201 · Cited by 2
The Role of Resistance in Candida Infections: Epidemiology and Treatment
Sobel, J. D., & Akins, R. A. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-595-8_18 · Cited by 2
A Case of Micafungin-Hyposensitive Candida glabrata Due to FKS2 Gene Mutation
Inui, S., Nakamura, T., Tanabe, K., Ohno, H., Koike, C., Okuda, K., Nakata, C., FUJIMOTO, H., Ohkura, H., Miyazaki, Y., et al. (2011) · Kansenshogaku zasshi · doi:10.11150/kansenshogakuzasshi.85.49 · Cited by 2
Mechanisms of Resistance to Antifungal Agents
Perlin, D. S. (2023) · ClinMicroNow · doi:10.1002/9781683670438.mcm0134 · Cited by 2
Self-citationHsu, L.-H., Chou, Y. Y., Shen, T., Wieczorek, D., & Chen, Y. (2025) · Virulence · doi:10.1080/21505594.2025.2609407 · Cited by 1
Angiolini, S. C., Rodríguez, E., Manzone-Rodríguez, C., Icely, P. A., Miró, M. S., Abiega, C. D., Riera, F. O., Iribarren, P., Caeiro, J. P., & Sotomayor, C. E. (2026) · Medical Mycology · doi:10.1093/mmy/myag028 · Cited by 1
Liu, W., Hiroki, S., Li, S., Isuhuaylas, L. A. V., Yamanaka, D., Itto‐Nakama, K., Noda, Y., Boone, C. M., Yashiroda, Y., & Ohya, Y. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.03630-25 · Cited by 1
Clinical Relevance of In Vitro Resistance of Echinocandins: a Focus on Candida parapsilosis
Kale-Pradhan, P. B., Wilhelm, S. M., & Johnson, L. B. (2012) · Current Fungal Infection Reports · doi:10.1007/s12281-012-0087-9 · Cited by 1
Résistance des Candida aux antifongiques : détection et mécanismes
Dannaoui, É. (2013) · Revue Francophone des Laboratoires · doi:10.1016/s1773-035x(13)71948-8 · Cited by 1
Treatment of Candida Glabrata With Micafungin: A Case Report and Brief Review of the Literature
Guleri, A., Gatt, D., Sharma, R., & Pettit, S. (2013) · Journal of Medical Cases · doi:10.4021//jmc.v4i6.1237 · Cited by 1
Current Controversies in the Treatment of Fungal Infections
Pfeiffer, C. D., Perfect, J. R., & Alexander, B. D. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-644-3_27 · Cited by 1
Role of Glucan-Derived Polymers in the Pathogenic Fungus Candida albicans
Prieto, D., Román, E., Alonso‐Monge, R., & Plá, J. (2019) · Biologically-inspired systems · doi:10.1007/978-3-030-12919-4_9 · Cited by 1
Some issues of the resistance of Candida glabrata to echinocandins
Veselov, A. V. (2019) · Clinical Microbiology and Antimicrobial Chemotherapy · doi:10.36488/cmac.2019.4.324-329 · Cited by 1
Drug resistance in pathogenic species of Candida
Jaiswal, N., & Kumar, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91643-1.00014-4 · Cited by 1
Use of Novel Tools to Probe Drug Resistance in Fungi
Zhao, Y., & Perlin, D. S. (2017) · Springer eBooks · doi:10.1007/978-1-4939-0694-9_21 · Cited by 1
Self-citationInhibition of Ras1-MAPK pathways for hypha formation by novel drug candidates in Candida albicansPreprint
Park, Y. K., Shin, J., Lee, H., Kim, H. D., & Kim, J. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.06.451239 · Cited by 1
Doorley, L. A. (2023) · doi:10.21007/etd.cghs.2023.0620 · Cited by 1
Mechanisms of Resistance to Antifungal Agents
Perlin, D. S. (2023) · ClinMicroNow · doi:10.1002/9781683674849.mcm0134 · Cited by 1
Self-citationAccoceberry, I., Lefranc, M., Meunier, C., Quilès, F., Kordalewska, M., Biteau, N., Perlin, D. S., El‐Kirat‐Chatel, S., & Noël, T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.08.647726 · Cited by 1
Self-citationFungal Drug Resistance and Pharmacologic Considerations of Dosing Newer Antifungal Therapies
Lewis, R. E., & Perlin, D. S. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-644-3_28
Self-citationGenetic Basis of Candida Biofilm Resistance Due to Drug-Sequestering
Nett, J. E., Sánchez, H., Cain, M. T., & Andes, D. R. (2010)
Rapid Antifungal Susceptibility Testing by Matrix-Assisted Laser Desorption Ionization Time-of- 1
Vella, A., Carolis, E. D., Perlin, D. S., Posteraro, B., Sanguinetti, M., & Bruker, D. (2013)
Self-citationThe Roles of Hsp90 and Calcineurin in Antifungal Drug Resistance
Singh, S. (2012) · TSpace (University of Toronto)
Antifungal Consideration for Transplant Recipients
Dubrovskaya, Y., Merl, M. Y., Perlin, D. S., & Safdar, A. (2019) · Springer eBooks · doi:10.1007/978-1-4939-9034-4_52
Self-citationThe Research Progress on Occurrence of Candida Drug Resistance
付, 婉. (2017) · Advances in Microbiology · doi:10.12677/amb.2017.64013
Use of Novel Tools to Probe Drug Resistance in Fungi
Zhao, Y., & Perlin, D. S. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0667-3_21-1
Self-citationPerlin, D. S. (2017) · Springer eBooks · doi:10.1007/978-3-319-46718-4_29
Self-citationSamanta, I., & Bandyopadhyay, S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815770-1.00026-2
MDR in Candida: The Real Storm
Srivastava, P., Tiwari, S., Kumar, M., Murhekar, M. V., & Dwivedi, G. R. (2024) · Springer eBooks · doi:10.1007/978-981-97-4909-6_4
Ghosh, S., Sarkar, S., Garai, P., Maiti, A. K., Saha, N. C., & Banerjee, P. (2025) · Discover Applied Sciences · doi:10.1007/s42452-025-07493-1
L'interaction Hsp90/co-chaperonnes : nouvelle cible pour le traitement des candidoses invasives
Rouges, C. (2023) · theses.fr (ABES) · doi:10.70675/40b24a3fz159ez4d8ez8a34zdd8ffa1c22fa
A Mechanism Driving Echinocandin Heteroresistance in Candida glabrataPreprint
Harrington, A. A., & Cunningham, K. W. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.16.718912
Parallel evolution under constraint shapes echinocandin resistance in Candida aurisPreprint
Cauldron, N. C., Dort, E. N., Weeks, G., Rogers, P. D., & Cuomo, C. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.30.748140
A gene network regulating echinocandin heteroresistance in Candida glabrata
Harrington, A. A., & Cunningham, K. W. (2026) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00549-26
Dual Peptide Modification via Isopeptide Bonding and Lipidation Boosts Antifungal Activity
Hur, D. B., Wani, N. A., Stolovicki, E., Kluzek, M., Abramson, J., & Shai, Y. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01856
Metadata
- Authors
- Garcia-Effron, G., Park, S., & Perlin, D. S.
- Affiliations
- Public Health Research Institute, New Jersey Medical School-UMDNJ, Newark, New Jersey 07103
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Perlin, David S.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2009-01
- Volume
- 53
- Issue
- 1
- Pages
- 112-122
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC2612148
- OpenAlex
- W2116629209
- Cited by
- 256
- References
- 55
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 4 · 2023: 17 · 2022: 4 · 2021: 10 · 2020: 8 · 2019: 13 · 2018: 12 · 2017: 19 · 2016: 8 · 2015: 10 · 2014: 16 · 2013: 17 · 2012: 18
- FWCI
- 17.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Astellas Pharma
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI069397)
- 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 › Plant Science › Fungal Plant Pathogen Control
- Keywords
- echinocandins, Candida albicans, FKS1 mutations, 1,3-β-D-glucan synthase, enzyme kinetics, caspofungin, micafungin, anidulafungin, susceptibility breakpoints, antifungal resistance, serum interference, clinical isolates
- MeSH terms
- Caspofungin, Micafungin, Anidulafungin, Candida albicans, Fungal Proteins, Glucosyltransferases, Microbial Sensitivity Tests, Echinocandins, Lipopeptides
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
