白念珠菌对棘白菌素类药物耐药机制的研究进展

doi:10.35541/cjd.20210273

Abstract

Abstract: 【Abstract】 With the application of echinocandin antifungals, more and more resistant Candida albicans strains have been detected. It has been reported that mechanisms underlying the resistance of Candida albicans to echinocandin antifungals mainly involve FKS, MSH2 and ERG3 gene mutations, biofilm formation, cellular stress response, compensatory increases in chitin, sphingolipid synthesis, etc. This review focuses on echinocandin resistance-related genes and underlying mechanisms in Candida albicans, which will help to overcome and prevent echinocandin resistance in clinical practice, and explore new therapeutic targets and drugs for Candida albicans infection.

Key words: Candida albicans, Antifungal drug resistance, Echinocandin, Point mutations, FKS

Yang Lu, Duan Zhimin, Li Min. Mechanisms underlying the resistance of Candida albicans to echinocandin antifungals[J]. Chinese Journal of Dermatology, 2022, 55(12): 1114-1117.doi:10.35541/cjd.20210273

References ［34］

［1］	Lee Y, Puumala E, Robbins N, et al. Antifungal drug resistance: molecular mechanisms in Candida albicans and beyond［J］. Chem Rev, 2021,121（6）:3390⁃3411. doi: 10.1021/acs.chemrev. 0c00199.
［2］	Mesini A, Mikulska M, Giacobbe DR, et al. Changing epidemiology of candidaemia: increase in fluconazole⁃resistant Candida parapsilosis［J］. Mycoses, 2020,63（4）:361⁃368. doi: 10.1111/myc.13050.
［3］	Coste AT, Kritikos A, Li J, et al. Emerging echinocandin⁃resistant Candida albicans and glabrata in Switzerland［J］. Infection, 2020,48（5）: 761⁃766. doi: 10.1007/s15010⁃020⁃01475⁃8.
［4］	Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America［J］. Clin Infect Dis, 2016,62（4）:e1⁃50. doi: 10.1093/cid/civ933.
［5］	Pappas PG. Invasive candidiasis［J］. Infect Dis Clin North Am, 2006,20（3）:485⁃506. doi: 10.1016/j.idc.2006.07.004.
［6］	Shields RK, Nguyen MH, Press EG, et al. Abdominal candidiasis is a hidden reservoir of echinocandin resistance［J］. Antimicrob Agents Chemother, 2014,58（12）:7601⁃7605. doi: 10.1128/AAC. 04134⁃14.
［7］	Shields RK, Nguyen MH, Press EG, et al. 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［J］. Antimicrob Agents Chemother, 2012,56（9）:4862⁃4869. doi: 10.1128/AAC.00027⁃12.
［8］	Perlin DS. Mechanisms of echinocandin antifungal drug resistance［J］. Ann N Y Acad Sci, 2015,1354（1）:1⁃11. doi: 10. 1111/nyas.12831.
［9］	Pristov KE, Ghannoum MA. Resistance of Candida to azoles and echinocandins worldwide［J］. Clin Microbiol Infect, 2019,25（7）:792⁃798. doi: 10.1016/j.cmi.2019.03.028.
［10］	Bowman SM, Free SJ. The structure and synthesis of the fungal cell wall［J］. Bioessays, 2006,28（8）:799⁃808. doi: 10.1002/bies.20441.
［11］	Lee KK, Kubo K, Abdelaziz JA, et al. Yeast species⁃specific,differential inhibition of β⁃1,3⁃glucan synthesis by poacic acid and caspofungin［J］. Cell Surf, 2018,3:12⁃25. doi: 10.1016/j.tcsw.2018.09.001.
［12］	Antinori S, Milazzo L, Sollima S, et al. Candidemia and invasive candidiasis in adults: a narrative review［J］. Eur J Intern Med, 2016,34:21⁃28. doi: 10.1016/j.ejim.2016.06.029.
［13］	Lim HJ, Shin JH, Kim MN, et al. Evaluation of two commercial broth microdilution methods using different interpretive criteria for the detection of molecular mechanisms of acquired azole and echinocandin resistance in four common Candida species［J］. Antimicrob Agents Chemother, 2020,64（11）:e00740⁃20. doi: 10.1128/AAC.00740⁃20.
［14］	Spettel K, Barousch W, Makristathis A, et al. Analysis of antifungal resistance genes in Candida albicans and Candida glabrata using next generation sequencing［J/OL］. PLoS One, 2019,14（1）:e0210397［2021⁃01⁃05］. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328131/. doi: 10.1371/journal.pone.0210397.
［15］	Garcia⁃Effron G, Park S, Perlin DS. Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints［J］. Antimicrob Agents Chemother, 2009,53（1）:112⁃122. doi: 10. 1128/AAC.01162⁃08.
［16］	Logan C, Martin⁃Loeches I, Bicanic T. Invasive candidiasis in critical care: challenges and future directions［J］. Intensive Care Med, 2020,46（11）:2001⁃2014. doi: 10.1007/s00134⁃020⁃06240⁃x.
［17］	Sitterlé E, Coste AT, Obadia T, et al. Large⁃scale genome mining allows identification of neutral polymorphisms and novel resistance mutations in genes involved in Candida albicans resistance to azoles and echinocandins［J］. J Antimicrob Chemother, 2020,75（4）: 835⁃848. doi: 10.1093/jac/dkz537.
［18］	Arendrup MC, Park S, Brown S, et al. Evaluation of CLSI M44⁃A2 disk diffusion and associated breakpoint testing of caspofungin and micafungin using a well⁃characterized panel of wild⁃type and fks hot spot mutant Candida isolates［J］. Antimicrob Agents Chemother, 2011,55（5）:1891⁃1895. doi: 10. 1128/AAC.01373⁃10.
［19］	Cheung YY, Hui M. Effects of Echinocandins in combination with nikkomycin Z against invasive Candida albicans bloodstream isolates and the FKS mutants［J］. Antimicrob Agents Chemother, 2017,61（11）: e00619⁃17. doi: 10.1128/AAC. 00619⁃17.
［20］	Shields RK, Nguyen MH, Press EG, et al. Rate of FKS mutations among consecutive Candida isolates causing bloodstream infection［J］. Antimicrob Agents Chemother, 2015,59（12）:7465⁃7470. doi: 10.1128/AAC.01973⁃15.
［21］	Sanguinetti M, Posteraro B, Lass⁃Flörl C. Antifungal drug resistance among Candida species: mechanisms and clinical impact［J］. Mycoses, 2015,58（S2）:2⁃13. doi: 10.1111/myc.12330.
［22］	Forche A, Abbey D, Pisithkul T, et al. Stress alters rates and types of loss of heterozygosity in Candida albicans［J］. mBio, 2011,2（4）: e00129⁃11. doi: 10.1128/mBio.00129⁃11.
［23］	Suwunnakorn S, Wakabayashi H, Kordalewska M, et al. FKS2 and FKS3 genes of opportunistic human pathogen Candida albicans influence echinocandin susceptibility［J］. Antimicrob Agents Chemother, 2018,62（4）:e02299⁃17. doi: 10.1128/AAC. 02299⁃17.
［24］	Katiyar SK, Alastruey⁃Izquierdo A, Healey KR, et al. Fks1 and Fks2 are functionally redundant but differentially regulated in Candida glabrata: implications for echinocandin resistance［J］. Antimicrob Agents Chemother, 2012,56（12）:6304⁃6309. doi: 10. 1128/AAC.00813⁃12.
［25］	Healey KR, Zhao Y, Perez WB, et al. Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi⁃drug resistance［J］. Nat Commun, 2016,7:11128. doi: 10.1038/ncomms11128.
［26］	Rybak JM, Dickens CM, Parker JE, et al. Loss of C⁃5 sterol desaturase activity results in increased resistance to azole and echinocandin antifungals in a clinical isolate of Candida parapsilosis［J］. Antimicrob Agents Chemother, 2017,61（9）:e00651⁃17. doi: 10.1128/AAC.00651⁃17.
［27］	Niimi K, Maki K, Ikeda F, et al. Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility［J］. Antimicrob Agents Chemother, 2006,50（4）:1148⁃1155. doi: 10.1128/AAC.50.4.1148⁃ 1155.2006.
［28］	Pfaller MA, Castanheira M, Lockhart SR, et al. Frequency of decreased susceptibility and resistance to echinocandins among fluconazole⁃resistant bloodstream isolates of Candida glabrata［J］. J Clin Microbiol, 2012,50（4）:1199⁃1203. doi: 10.1128/JCM. 06112⁃11.
［29］	Vediyappan G, Rossignol T, d′Enfert C. Interaction of Candida albicans biofilms with antifungals: transcriptional response and binding of antifungals to beta⁃glucans［J］. Antimicrob Agents Chemother, 2010,54（5）:2096⁃2111. doi: 10.1128/AAC.01638⁃09.
［30］	Shor E, Perlin DS. Coping with stress and the emergence of multidrug resistance in fungi［J/OL］. PLoS Pathog, 2015,11（3）:e1004668［2021⁃01⁃10］. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366371/. doi: 10.1371/journal.ppat.1004668.
［31］	Accoceberry I, Couzigou C, Fitton⁃Ouhabi V, et al. Challenging SNP impact on caspofungin resistance by full⁃length FKS1 allele replacement in Candida lusitaniae［J］. J Antimicrob Chemother, 2019,74（3）:618⁃624. doi: 10.1093/jac/dky475.
［32］	Healey KR, Katiyar SK, Raj S, et al. CRS⁃MIS in Candida glabrata: sphingolipids modulate echinocandin⁃Fks interaction［J］. Mol Microbiol, 2012,86（2）:303⁃313. doi: 10.1111/j.1365⁃2958.2012.08194.x.
［33］	Garnaud C, García⁃Oliver E, Wang Y, et al. The rim pathway mediates antifungal tolerance in Candida albicans through newly identified Rim101 transcriptional targets, including Hsp90 and Ipt1［J］. Antimicrob Agents Chemother, 2018,62（3）:e01785⁃17. doi: 10.1128/AAC.01785⁃17.
［34］	Gonzalez⁃Lara MF, Ostrosky⁃Zeichner L. Invasive candidiasis［J］. Semin Respir Crit Care Med, 2020,41（1）:3⁃12. doi: 10. 1055/s⁃0040⁃1701215.

[1]	Zhang Ruijun, Su Xiaorui, Li Ting, He Xiao, Yang Yuanwen, Kang Yuying, . Analysis of pathogens of mucosal candidiasis and their resistance to drugs in a third-grade class-A hospital in Taiyuan, Shanxi [J]. Chinese Journal of Dermatology, 2023, 56(1): 56-58.
[2]	Ding Tiantian, Cui Baohong, Mi Shuhong, Zhang Yang, Zheng Hailin, Shi Jihai, Liu Weida. Comparison of drug susceptibility of and drug resistance mutations in fluconazole-resistant Candida albicans strains from superficial and deep infections [J]. Chinese Journal of Dermatology, 2022, 55(10): 874-878.
[3]	Yang Rui, Kong Qingtao, Xu Jie, Zhang Chen, Sang Hong. Screening of susceptibility genes and an immunological study in a patient with recurrent cervical lymphadenitis caused by Candida albicans [J]. Chinese Journal of Dermatology, 2022, 55(1): 50-54.
[4]	Lin Zehang, Duan Zhimin, Xu Song, Chen Xu, Li Min. Regulatory effect of Candida albicans hyphae on the key autophagy-related molecule microtubule-associated protein 1 light chain 3 in murine bone marrow-derived macrophages [J]. Chinese Journal of Dermatology, 2021, 54(3): 189-195.
[5]	Wang Ruojun, Li Ruoyu. Adverse reactions to interleukin-17A and its receptor antagonists in the treatment of psoriasis [J]. Chinese Journal of Dermatology, 2021, 54(2): 170-173.
[6]	. In vitro inhibitory effect of Fe3O4 nanozymes against Candida albicans [J]. Chinese Journal of Dermatology, 2020, 53(7): 554-556.
[7]	Lyu Yan, Zhang Yanli, Zhang Zhanpeng, Zhao Yajing, Zhang Yishan, Li Shuixiu, Zhang Hong. ATP1 promotes Candida albicans to escape from macrophage killing through regulating oxidative stress [J]. Chinese Journal of Dermatology, 2020, 53(7): 519-524.
[8]	. Roles of Dectin-1 in phagocytosis of Candida albicans by macrophage-like cells derived from a human acute monocytic leukemia cell line THP-1 [J]. Chinese Journal of Dermatology, 2018, 51(6): 425-428.
[9]	. Relationship between phospholipase expression and fluconazole resistance in Candida albicans [J]. Chinese Journal of Dermatology, 2010, 43(9): 641-644.
[10]	. Detection of TAC1 gene point mutations in fluconazole-resistant Candida albicans isolates with rolling circle amplification [J]. Chinese Journal of Dermatology, 2010, 43(8): 529-533.
[11]	. Study of biofilm formation by Trichosporon asahii [J]. Chinese Journal of Dermatology, 2010, 43(8): 538-541.
[12]	Yan Xiaofeng . Expression of stroma-derived factor 1 and its receptor CXCR4 in a murine model of vaginal candidiasis [J]. Chinese Journal of Dermatology, 2008, 41(8): 504-508.
[13]	QIN Xiao-feng, WU Jian-hua, HUANG Yi, JIANG Yuan-ying, GU Jun. Relationship between the expression of multidrug resistant protein genes and fluconazole resistance in clinical isolates of Candida albieans [J]. Chinese Journal of Dermatology, 2007, 40(8): 482-484.
[14]	JIANG Hong-hao, ZHANG Hong, QIAO Jian-jun, HE Han-yan, GAO Ai-li. Difference of ERG11 gene between hyphal and yeast forms of Candida albieans [J]. Chinese Journal of Dermatology, 2007, 40(4): 217-220.
[15]	XU Yong-hao, LI Chun-yang, CHEN La-mei, HU Qin-feng. Correlation between antifungal susceptibility of clinical isolates of Candida albicans to fluconazole and ERG11 mutations [J]. Chinese Journal of Dermatology, 2007, 40(12): 756-758.

Mechanisms underlying the resistance of Candida albicans to echinocandin antifungals

PDF

PDF (Mobile)

Knowledge

Abstract

Cite this article

share this article

References ［34］

Related Articles 15

Metrics

Comments

Recommended 10