Comparative analyses of the biological characteristics, fluconazole resistance, and heat adaptation mechanisms of Candida auris and members of the Candida haemulonii complex

对耳念珠菌和血红念珠菌复合群成员的生物学特性、氟康唑耐药性和热适应机制进行比较分析

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Abstract

Candida auris and the emerging fungal pathogens comprising the Candida haemulonii complex (C. haemulonii and C. duobushaemulonii) are phylogenetically closely related. Notably, each can cause serious nosocomial infection and acquire multidrug resistance. We isolated various strains of C. auris and C. haemulonii complex from patient specimens. The results of growth curve analysis and the spot assay showed that C. auris was the most tolerant to high temperatures, while differences were found among the five strains of the C. haemulonii complex. We selected a representative strain from each of the three types of fungi that exhibit differences in heat resistance for further research. In addition, three strains were resistant to fluconazole, whereas sensitivity to common antifungal agents differed, as determined by the micro liquid-based dilution method. Moreover, C. auris was more virulent in Galleria mellonella than members of the C. haemulonii complex. In addition, there were notable differences in biofilm formation, hydrophobicity, adhesion, and enzyme activity among the three Candida strains. The results of transcriptomics, real-time quantitative PCR, and biochemical analyses showed that C. auris was most tolerant to heat stress due to the expression of genes in regulating pyruvate consumption and the accumulation of intracellular pyruvate. These results provide valuable references for further studies of the biological characteristics, pathogenesis, and treatment of Candida infection. IMPORTANCE: Candida auris and the Candida haemulonii complex are multidrug-resistant fungi that have emerged in recent years, posing a significant threat to human health. The biological characteristics of two strains of the Candida haemulonii complex and one strain of C. auris isolated from clinical patient samples were analyzed. Our primary focus was to compare the heat resistance between C. auris and the C. haemulonii complex, with a particular emphasis on understanding the differences in the heat resistance mechanisms. The main distinction between environmental and pathogenic fungi is that the latter can survive at human body temperature. Despite their close phylogenetic relationship, the C. haemulonii complex and C. auris exhibit significant differences in heat resistance. Studying these heat resistance mechanisms may aid in our understanding of the evolutionary process of environmental fungi transforming into pathogenic fungi.

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