Department of Medical Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Mycopathologia. 2021 Dec;186(6):847-856. doi: 10.1007/s11046-021-00580-y. Epub 2021 Aug 19.
Limited knowledge exists on the virulence factors of Candida tropicalis and the mechanisms of azole resistance that lead to an intensified pathogenicity and treatment failure. We aimed to evaluate the virulence factors and molecular mechanisms of azole resistance among C. tropicalis isolated from patients with candidemia.
Several virulence factors, including extracellular enzymatic activities, cell surface hydrophobicity (CSH), and biofilm formation, were evaluated. Antifungal susceptibility pattern and expression level of ERG11, UPC2, MDR1, and CDR1 genes of eight (4 fluconazole resistance and 4 fluconazole susceptible) clinical C. tropicalis isolates were assessed. The correlation between the virulence factors and antifungal susceptibility patterns was analyzed.
During a 4 year study, forty-five C. tropicalis isolates were recovered from candidemia patients. The isolates expressed different frequencies of virulence determinants as follows: coagulase 4 (8.9%), phospholipase 5 (11.1%), proteinase 31 (68.9%), esterase 43 (95.6%), hemolysin 44 (97.8%), biofilm formation 45 (100%) and CSH 45(100%). All the isolates were susceptible to amphotericin B and showed the highest resistance to voriconazole. There was a significant positive correlation between micafungin minimum inhibitory concentrations (MICs) and hemolysin production (r = 0.316). However, we found a negative correlation between fluconazole MICs and esterase production (r = -0.383). We observed the high expression of ERG11 and UPC2 genes in fluconazole-resistant C. tropicalis isolates.
C. tropicalis isolated from candidemia patients extensively displayed capacities for biofilm formation, hemolysis, esterase activity, and hydrophobicity. In addition, the overexpression of ERG11 and UPC2 genes was considered one of the possible mechanisms of azole resistance.
关于热带假丝酵母菌的毒力因子和导致致病性增强及治疗失败的唑类耐药机制的知识有限。我们旨在评估从念珠菌血症患者中分离的热带假丝酵母菌的毒力因子和唑类耐药的分子机制。
评估了几种毒力因子，包括细胞外酶活性、细胞表面疏水性（CSH）和生物膜形成。评估了 8 株（4 株氟康唑耐药和 4 株氟康唑敏感）临床热带假丝酵母菌分离株的抗真菌药敏谱和 ERG11、UPC2、MDR1 和 CDR1 基因的表达水平。分析了毒力因子与抗真菌药敏谱之间的相关性。
在 4 年的研究中，从念珠菌血症患者中分离出 45 株热带假丝酵母菌。这些分离株表现出不同频率的毒力决定因素，如下所示：凝固酶 4（8.9%）、磷脂酶 5（11.1%）、蛋白酶 31（68.9%）、酯酶 43（95.6%）、溶血素 44（97.8%）、生物膜形成 45（100%）和 CSH 45（100%）。所有分离株均对两性霉素 B敏感，对伏立康唑的耐药性最高。微小管囊菌素最小抑菌浓度（MICs）与溶血素产生之间存在显著正相关（r=0.316）。然而，我们发现氟康唑 MICs 与酯酶产生之间存在负相关（r=-0.383）。我们观察到氟康唑耐药的热带假丝酵母菌分离株中 ERG11 和 UPC2 基因的高表达。
从念珠菌血症患者中分离的热带假丝酵母菌广泛具有生物膜形成、溶血、酯酶活性和疏水性的能力。此外，ERG11 和 UPC2 基因的过表达被认为是唑类耐药的可能机制之一。
