Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Candida Species

被引:40
作者
Czajka, Karolina M. [1 ]
Venkataraman, Krishnan [1 ,2 ]
Brabant-Kirwan, Danielle [3 ]
Santi, Stacey A. [3 ]
Verschoor, Chris [1 ,2 ,3 ]
Appanna, Vasu D. [2 ]
Singh, Ravi [1 ,3 ]
Saunders, Deborah P. [1 ,3 ]
Tharmalingam, Sujeenthar [1 ,2 ,3 ]
机构
[1] NOSM Univ, Med Sci Div, 935 Ramsey Lake Rd, Sudbury, ON P3E 2C6, Canada
[2] Laurentian Univ, Sch Nat Sci, Sudbury, ON P3E 2C6, Canada
[3] Hlth Sci North Res Inst, Sudbury, ON P3E 2H2, Canada
关键词
antifungal; resistance; Candida; azoles; polyenes; echinocandins; fluorouracil; gene mutations; fungal infection; mutations; minimal inhibitory concentration; ergosterol; cell wall; efflux pumps; transporters; LIPOSOMAL AMPHOTERICIN-B; AMINO-ACID SUBSTITUTIONS; OF-FUNCTION MUTATIONS; EFFLUX PUMP ACTIVITY; FLUCONAZOLE RESISTANCE; AZOLE RESISTANCE; BIOFILM FORMATION; DRUG-RESISTANCE; CELL-WALL; IN-VITRO;
D O I
10.3390/cells12222655
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance.
引用
收藏
页数:33
相关论文
共 252 条
  • [1] An update on antifungal targets and mechanisms of resistance in Candida albicans
    Akins, RA
    [J]. MEDICAL MYCOLOGY, 2005, 43 (04) : 285 - 318
  • [2] Antifungal drug susceptibility, molecular basis of resistance to echinocandins and molecular epidemiology of fluconazole resistance among clinical Candida glabrata isolates in Kuwait
    Al-Baqsami, Zahraa F.
    Ahmad, Suhail
    Khan, Ziauddin
    [J]. SCIENTIFIC REPORTS, 2020, 10 (01)
  • [3] Biofilm matrix of Candida albicans and Candida tropicalis:: chemical composition and role in drug resistance
    Al-Fattani, Mohammed A.
    Douglas, L. Julia
    [J]. JOURNAL OF MEDICAL MICROBIOLOGY, 2006, 55 (08) : 999 - 1008
  • [4] The bZip transcription factor Cap1p is involved in multidrug resistance and oxidative stress response in Candida albicans
    Alarco, AM
    Raymond, M
    [J]. JOURNAL OF BACTERIOLOGY, 1999, 181 (03) : 700 - 708
  • [5] Increasing Echinocandin Resistance in Candida glabrata: Clinical Failure Correlates With Presence of FKS Mutations and Elevated Minimum Inhibitory Concentrations
    Alexander, Barbara D.
    Johnson, Melissa D.
    Pfeiffer, Christopher D.
    Jimenez-Ortigosa, Cristina
    Catania, Jelena
    Booker, Rachel
    Castanheira, Mariana
    Messer, Shawn A.
    Perlin, David S.
    Pfaller, Michael A.
    [J]. CLINICAL INFECTIOUS DISEASES, 2013, 56 (12) : 1724 - 1732
  • [6] Drug susceptibility profile of Candida glabrata clinical isolates from Iran and genetic resistant mechanisms to caspofungin
    Amanloo, Saeid
    Shams-Ghahfarokhi, Masoomeh
    Ghahri, Mohammad
    Razzaghi-Abyaneh, Mehdi
    [J]. REVISTA IBEROAMERICANA DE MICOLOGIA, 2018, 35 (02): : 88 - 91
  • [7] Anderson JB, 2003, GENETICS, V163, P1287
  • [8] Development and characterization of an in vivo central venous catheter Candida albicans biofilm model
    Andes, D
    Nett, J
    Oschel, P
    Albrecht, R
    Marchillo, K
    Pitula, A
    [J]. INFECTION AND IMMUNITY, 2004, 72 (10) : 6023 - 6031
  • [9] [Anonymous], 2020, Epidemiological Cutoff Values for Antifungal Susceptibility Testing, V3rd
  • [10] [Anonymous], 2019, CdcAntibiotic Resistance Threats in the United States, 2019