Sharma Vrinda, Das Sourav, Spruijtenburg Bram, de Groot Theun, Meijer Eelco, Kaur Harsimran, Rudramurthy Shivaprakash M, Ghosh Anup
Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Centre of Expertise for Mycology, Radboud University Medical Centre-CWZ, Nijmegen, the Netherlands.
Mycoses. 2025 May;68(5):e70062. doi: 10.1111/myc.70062.
The recent rise in the global incidence of fluconazole resistance in C. parapsilosis has become a significant public health concern. Epidemiological studies suggest that fluconazole resistance in C. parapsilosis spreads through endemic clones. We, therefore, investigated the molecular epidemiology of fluconazole-resistant C. parapsilosis in our centre.
C. parapsilosis isolates from 2016 through 2022 were investigated for antifungal susceptibility. Fluconazole-resistant isolates were analysed for ERG11 mutation using Sanger sequencing. Gene expression profiles of ERG11, CDR1 and MDR1 were assessed by real-time qPCR. The epidemiological relationship of resistant and susceptible isolates of C. parapsilosis was investigated using short tandem repeat typing. Additionally, biofilm production and cell wall ergosterol contents were also quantified and compared.
Among 572 C. parapsilosis isolates, 48 (8.4%) were resistant to fluconazole. Of 28 recoverable resistant isolates, 17.9% (5/28) were wild-type and 82.1% (23/28) harboured the following ERG11 mutations: Y132F (n = 3), K143R (n = 10) and K143R + R398I (10/28). Significant fold-changes were observed in ERG11 (p = 0.037) and MDR1 (p = 0.008) gene expressions in fluconazole resistant compared to susceptible isolates. Contrary to global reports, STR typing suggested a limited clonal transmission of resistant C. parapsilosis with multiple introductions of resistant isolates in our centre. On fluconazole exposure, ergosterol content significantly increased (p < 0.01) in resistant isolates, particularly in isolates harbouring ERG11 mutations. In contrast, fluconazole-susceptible isolates formed comparatively higher baseline biofilm (p < 0.05) than resistant isolates with ERG11 mutation.
The current study underscores the need for continuous molecular surveillance and tailored therapeutic options for effective management of fluconazole resistance in C. parapsilosis.
近年来，近平滑念珠菌对氟康唑的耐药率在全球范围内呈上升趋势，已成为一个重大的公共卫生问题。流行病学研究表明，近平滑念珠菌对氟康唑的耐药性通过地方流行克隆株传播。因此，我们对本中心耐氟康唑近平滑念珠菌的分子流行病学进行了调查。
对2016年至2022年分离出的近平滑念珠菌进行抗真菌药敏试验。采用桑格测序法分析耐氟康唑菌株的ERG11基因突变情况。通过实时定量PCR评估ERG11、CDR1和MDR1的基因表达谱。采用短串联重复序列分型法研究近平滑念珠菌耐药株与敏感株之间的流行病学关系。此外，还对生物膜的产生和细胞壁麦角甾醇含量进行了定量和比较。
在572株近平滑念珠菌中，48株（8.4%）对氟康唑耐药。在28株可恢复的耐药菌株中，17.9%（5/28）为野生型，82.1%（23/28）存在以下ERG11突变：Y132F（n = 3）、K143R（n = 10）和K143R + R398I（10/28）。与敏感菌株相比，耐氟康唑菌株的ERG11（p = 0.037）和MDR1（p = 0.008）基因表达有显著的倍数变化。与全球报告相反，STR分型表明，本中心耐药近平滑念珠菌的克隆传播有限，有多个耐药菌株传入。在接触氟康唑后，耐药菌株，尤其是存在ERG11突变的菌株，其麦角甾醇含量显著增加（p < 0.01）。相比之下，氟康唑敏感菌株形成的基线生物膜比存在ERG11突变的耐药菌株更高（p < 0.05）。
本研究强调了持续进行分子监测和制定针对性治疗方案以有效管理近平滑念珠菌对氟康唑耐药性的必要性。
