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Prevalence and molecular basis of resistance to echinocandins among clinical Candida glabrata isolates in Guangdong province, China

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Lin, Weihong, Peng, Yaqin, Xiang, Bo, Fang, Jingchun, Ye, Junkai, Guo, Penghao·2025·BMC Microbiology
DOI 10.1186/s12866-025-04275-yPMC PMC12366116
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Abstract

BACKGROUND: Infections caused by Candida glabrata have raised increasing concerns, particularly due to the increasing resistance to echinocandins. OBJECTIVES: This study investigated echinocandins susceptibility trends in C. glabrata isolates and explored the mechanisms driving resistance. METHODS: We analyzed 418 strains of C. glabrata derived from hospitalized patients. Phenotypic resistance was assessed, and genotypic analysis was performed to identify mutations in the hotspot-1 and hotspot-2 regions of the FKS1 and FKS2 genes. Additionally, genotyping was conducted using multilocus sequence typing (MLST). RESULTS: The resistance rates to caspofungin, anidulafungin, and micafungin were 5.0%, 3.8%, and 4.0%, respectively, while fluconazole resistance was observed in 9.6% of the strains. Notably, 1.0% of the strains demonstrated resistance to both fluconazole and echinocandins. Mutations in the FKS genes were identified in 11 strains, predominantly in the FKS2-HS1 region. The most prevalent mutation was the F659 deletion (54.54%, 6/11), followed by S663F (18.18%, 2/11). Other mutations, including F659S, F659Y, and S663P, were also detected. These 11 mutated strains were classified into six distinct sequence types (STs), with ST208 being the most prevalent. CONCLUSION: The resistance rate of C. glabrata to echinocandins has been increasing annually in Guangdong province. Echinocandin resistance is associated with mutations in the FKS2 gene.

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  • The clinical utility of caspofungin is increasingly compromised by emergence of non-susceptible strains.

    “However, the clinical utility of caspofungin is increasingly compromised by the emergence of non‐susceptible strains [5, 6].”

    From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in <i>Candida Glabrata</i> (2026) · cites this paper as [6]

    The Results (In vitro susceptibility testing analysis; page not provided) report that caspofungin non-susceptibility among clinical C. glabrata isolates rose from 2.8% to 10.5% between 2020 and 2023. The Discussion says rising resistance poses therapeutic challenges, but the study concerns isolates from Guangdong and does not directly measure caspofungin’s clinical utility or establish a broader trend. (LLM, conf=0.85)

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Research works printed but not linked: 34

  1. [2]Andes DR, Safdar N, Baddley JW, Alexander B, Brumble L, Freifeld A, et al. The epidemiology and outcomes of invasive Candida infections among organ transplant recipients in the united states: results of the Transplant-Associated infection surveillance network (TRANSNET). Transpl Infect Dis. 2016;18(6):921–31. 10.1111/tid.12696. 27643395 · DOI
  2. [3]Al-Baqsami ZF, Ahmad S, Khan Z. Antifungal drug susceptibility, molecular basis of resistance to echinocandins and molecular epidemiology of fluconazole resistance among clinical Candida glabrata isolates in Kuwait. Sci Rep. 2020;10(1):6238. 10.1038/s41598-020-63326-x. 32277126 PMC7148369 · DOI
  3. [5]Cornely OA, Sprute R, Bassetti M, Chen SC, Groll AH, et al. Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in Cooperation with ISHAM and ASM. Lancet Infect Dis. 2025;25(5):e280–93. 10.1016/S1473-3099(24)00749-7. 39956121 · DOI
  4. [6]Czajka KM, Venkataraman K, Brabant-Kirwan D, Santi SA, Verschoor C, Appanna VD, et al. Molecular mechanisms associated with antifungal resistance in pathogenic Candida species. Cells. 2023;12(22):2655. 10.3390/cells122226555. 37998390 PMC10670235 · DOI
  5. [9]Pham CD, Iqbal N, Bolden CB, Kuykendall RJ, Harrison LH, Farley MM, et al. Role of FKS mutations in Candida glabrata: MIC values, Echinocandin resistance, and multidrug resistance. Antimicrob Agents Chemother. 2014;58(8):4690–6. 10.1128/AAC.02428-14. 24890592 PMC4136002 · DOI
  6. [10]Zhao Y, Nagasaki Y, Kordalewska M, Press EG, Shields RK, Nguyen MH, et al. Rapid Detection of FKS-Associated Echinocandin Resistance in Candida glabrata. Antimicrob Agents Chemother. 2016;60(11):6573–7. 10.1128/AAC.01247-16. 27550360 PMC5075061 · DOI
  7. [11]Beyda ND, John J, Kilic A, Alam MJ, Lasco TM, Garey KW. FKS mutant Candida glabrata: risk factors and outcomes in patients with candidemia. Clin Infect Dis. 2014;59(6):819–25. 10.1093/cid/ciu407. 24879785 · DOI
  8. [12]Arastehfar A, Daneshnia F, Zomorodian K, Najafzadeh MJ, Khodavaisy S, Zarrinfar H, et al. Low level of antifungal resistance in Iranian isolates of Candida glabrata recovered from blood samples in a multicenter study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1. Antimicrob Agents Chemother. 2019;63(7):e02503–18. 10.1128/AAC.02503-18. 30936110 PMC6591624 · DOI
  9. [13]Klotz U, Schmidt D, Willinger B, Steinmann E, Buer J, Rath MF, Steinmann J. Echinocandin resistance and population structure of invasive Candida glabrata isolates from two university hospitals in Germany and Austria. Mycoses. 2016;59(5):312–8. 10.1111/myc.12472. 26806376 · DOI
  10. [15]Dodgson AR, Pujol C, Denning DW, Soll DR, Fox AJ. Multilocus sequence typing of Candida glabrata reveals geographically enriched clades. J Clin Microbiol. 2003;41(12):5709–17. 10.1128/JCM.41.12.5709-5717.2003. 14662965 PMC309006 · DOI
  11. [16]Hernández-Pabón JC, Tabares B, Gil Ó, Lugo-Sánchez C, Santana A, Barón A, Firacative C. Candida non-albicans and non-auris causing invasive candidiasis in a fourth-level hospital in Colombia: epidemiology, antifungal susceptibility, and genetic diversity. J Fungi. 2024;10(5): 326. 10.3390/jof10050326. PMC11122357 38786681 · DOI
  12. [17]Guinea J. Global trends in the distribution of Candida species causing candidemia. Clin Microbiol Infect. 2014;20(Suppl 6):5–10. 24506442
  13. [18]Xiao M, Sun ZY, Kang M, Guo DW, Liao K, Chen SC, China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study Group, et al. Five-Year National surveillance of invasive candidiasis: species distribution and Azole susceptibility from the China hospital invasive fungal surveillance net (CHIF-NET) study. J Clin Microbiol. 2018;56(7):e00577–18. 10.1128/JCM.00577-18. 29743305 PMC6018329 · DOI
  14. [19]Onishi J, Meinz M, Thompson J, Curotto J, Dreikorn S, Rosenbach M, et al. Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors. Antimicrob Agents Chemother. 2000;44(2):368–77. 10.1128/AAC.44.2.368-377.2000. 10639364 PMC89685 · DOI
  15. [20]Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017;17(12):e383–92. 10.1016/S1473-3099(17)30316-X. 28774698 · DOI · Paper page
  16. [22]Healey KR, Perlin DS. Fungal resistance to echinocandins and the MDR phenomenon in Candida glabrata. J Fungi. 2018;4(3): 105. 10.3390/jof4030105. PMC6162769 30200517 · DOI · Paper page
  17. [23]Khalifa HO, Arai T, Majima H, Watanabe A, Kamei K. Genetic basis of azole and echinocandin resistance in clinical Candida glabrata in Japan. Antimicrob Agents Chemother. 2020;64(9):e00783-20. 10.1128/AAC.00783-20. 32571826 PMC7449192 · DOI · Paper page
  18. [24]Hou X, Xiao M, Chen SC, Kong F, Wang H, Chu YZ, et al. Molecular epidemiology and antifungal susceptibility of Candida glabrata in China (August 2009 to July 2014): a multi-center study. Front Microbiol. 2017;8: 880. 10.3389/fmicb.2017.00880. 28588560 PMC5440528 · DOI
  19. [25]Bilal H, Shafiq M, Hou B, Islam R, Khan MN, Khan RU, Zeng Y. Distribution and antifungal susceptibility pattern of Candida species from mainland china: a systematic analysis. Virulence. 2022;13(1):1573–89. 10.1080/21505594.2022.2123325. 36120738 PMC9487756 · DOI · Paper page
  20. [26]Georgiou PC, Arendrup MC, Meletiadis J. Early phenotypic detection of fluconazole- and anidulafungin-resistant Candida glabrata isolates. J Antimicrob Chemother. 2022;77(6):1655–61. 10.1093/jac/dkac075. 35323941 PMC9840476 · DOI
  21. [27]Farmakiotis D, Kontoyiannis DP. Epidemiology of antifungal resistance in human pathogenic yeasts: current viewpoint and practical recommendations for management. International Journal of Antimicrobial Agents. 2017;50(3):318–24. 10.1016/j.ijantimicag. 28669831 · DOI
  22. [28]Morio F, Jensen RH, Le Pape P, Arendrup MC. Molecular basis of antifungal drug resistance in yeasts. Int J Antimicrob Agents. 2017;50(5):599–606. 10.1016/j.ijantimicag.2017.05.012. 28669835 · DOI · Paper page
  23. [30]Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M, Jones RN. Twenty years of the SENTRY antifungal surveillance program: results for Candida species from 1997–2016. Open Forum Infect Dis. 2019;6(Suppl 1):S79–94. 10.1093/ofid/ofy358. 30895218 PMC6419901 · DOI · Paper page
  24. [31]Katiyar S, Shiffrin E, Shelton C, Healey K, Vermitsky JP, Edlind T. Evaluation of polymorphic locus sequence typing for Candida glabrata epidemiology. J Clin Microbiol. 2016;54(4):1042–50. 10.1128/JCM.03106-15. 26842706 PMC4809956 · DOI
  25. [32]Huang SJ, Lv G, Song YH, Zhao JT, Liu JY, Wang LL, Xiang MJ. Antifungal susceptibility, molecular epidemiology, and clinical risk factors of Candida glabrata in intensive care unit in a Chinese tertiary hospital. Front Cell Infect Microbiol. 2024;14:1455145. 10.3389/fcimb.2024.1455145. 39435186 PMC11491434 · DOI
  26. [34]Pfaller MA, Messer SA, Diekema DJ, Jones RN, Castanheira M. Use of micafungin as a surrogate marker to predict susceptibility and resistance to caspofungin among 3,764 clinical isolates of Candida by use of CLSI methods and interpretive criteria. J Clin Microbiol. 2014;52(1):108–14. 10.1128/JCM.02481-13. 24153129 PMC3911432 · DOI · Paper page
  27. [36]Shields RK, Nguyen MH, Press EG, Kwa AL, Cheng S, Du C, Clancy CJ. The presence of an FKS mutation rather than MIC is an independent risk factor for failure of Echinocandin therapy among patients with invasive candidiasis due to Candida glabrata. Antimicrob Agents Chemother. 2012;56(9):4862–9. 10.1128/AAC. 00027– 12. 22751546 PMC3421882 · DOI
  28. [37]Shabi Y, Russell-Tattrie A, Bharat A, Haldane D, Patriquin G. A pseudo-outbreak of Echinocandin-resistant Candida glabrata: the unreliability of Caspofungin testing in predicting Echinocandin susceptibility. J Assoc Med Microbiol Infect Dis Can. 2021;6(1):1–2. 10.3138/jammi-2020-0023. 36340217 PMC9612429 · DOI
  29. [38]Espinel-Ingroff A, Arendrup MC, Pfaller MA, Bonfietti LX, Bustamante B, Canton E, et al. Interlaboratory variability of Caspofungin mics for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? Antimicrob Agents Chemother. 2013;57(12):5836–42. 10.1128/AAC.01519-13. 24018263 PMC3837874 · DOI · Paper page
  30. [40]European Committee on Antimicrobial Susceptibility Testing (EUCAST). (2020). Breakpoint tables for interpretation of MICs for antifungal agents, version 10.0. Basel, CH: EUCAST. Retrieved from 10.2807/wd0060-2020 · DOI
  31. [41]Hou X, Xiao M, Wang H, Yu SY, Zhang G, Zhao Y, et al. Profiling of PDR1 and MSH2 in Candida glabrata bloodstream isolates from a multicenter study in China. Antimicrob Agents Chemother. 2018;62(6):e00153–18. 10.1128/AAC.00153-18. 29581110 PMC5971605 · DOI
  32. [42]Byun SA, Won EJ, Kim MN, Lee WG, Lee K, Lee HS, et al. Multilocus sequence typing (MLST) genotypes of Candida glabrata bloodstream isolates in Korea: association with antifungal resistance, mutations in mismatch repair gene (Msh2), and clinical outcomes. Front Microbiol. 2018;9:1523. 10.3389/fmicb.2018.01523. 30057573 PMC6053515 · DOI
  33. [43]Kiasat N, Rezaei-Matehkolaei A, Mahmoudabadi AZ. Microsatellite typing and antifungal susceptibility of Candida glabrata strains isolated from patients with Candida vaginitis. Front Microbiol. 2019;10:1678. 10.3389/fmicb.2019.01678. 31417505 PMC6685060 · DOI
  34. [44]Dhieb C, Normand AC, Al-Yasiri M, Chaker E, Euch E, Vranckx D, K., et al. MALDI-TOF typing highlights geographical and fluconazole resistance clusters in Candida glabrata. Med Mycol. 2015;53(5):462–9. 10.1093/mmy/myv013. 25841053 · DOI

Cited by

Sorted by citations

Authors
Lin, W., Peng, Y., Xiang, B., Fang, J., Ye, J., & Guo, P.
Affiliations
  • First Affiliated Hospital of Guangzhou Medical University (CN)
  • The First Affiliated Hospital, Sun Yat-sen University (CN)
Corresponding author
Guo, Penghao
ORCID
Venue
BMC Microbiology
Publisher
Springer Science and Business Media LLC
Published
2025-08-20
Volume
25
Issue
1
Pages
521-521
ISSN
1471-2180 (ISSN-L)
DOI
10.1186/s12866-025-04275-y
PMC
PMC12366116
OpenAlex
W4413365421
Cited by
3
References
7
Citations by year
2026: 2 · 2025: 1
FWCI
2.31
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Microbiology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Guangzhou Science and Technology Bureau Municipal School (Institute) Co-funded Project (202201020443)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida glabrata, echinocandin resistance, FKS1, FKS2, caspofungin, anidulafungin, micafungin, fluconazole resistance, antifungal resistance, multilocus sequence typing, sequence types, clinical isolates, Guangdong
MeSH terms
Antifungal Agents, Candidiasis, China, Female, Fungal Proteins, Genotype, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mutation, Prevalence, Drug Resistance, Fungal, Candida glabrata, Echinocandins, Multilocus Sequence Typing

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