The secreted acid trehalase encoded by the CgATH1 gene is involved in Candida glabrata virulence

BACKGROUND Candida glabrata yeast is the second cause of candidiasis worldwide. Differs from other yeasts since assimilates only glucose and trehalose (a characteristic used in rapid identification tests for this pathogen) by secreting into the medium a highly active acid trehalase encoded by the CgATH1 gene. OBJECTIVE This study aimed to characterise the function of the acid trehalase in the physiopathology of C. glabrata. METHODS Gene deletion was performed to obtain a mutant ath1Δ strain, and the ability of the ath1Δ strain to grow in trehalase, or the presence of trehalase activity in the ath1Δ yeast cells, was verified. We also tested the virulence of the ath1Δ strain in a murine model of infection. FINDINGS The ath1Δ mutant strain grows normally in the presence of glucose, but loses its ability to grow in trehalose. Due to the high acid trehalase activity present in wild-type cells, the cytoplasmic neutral trehalase activity is only detected in the ath1Δ strain. We also observed a significantly lower virulence of the ath1Δ strain in a murine model of infection with either normal or immunocompromised mice. MAIN CONCLUSIONS The acid trehalase is involved in the hydrolysis of external trehalose by C. glabrata, and the enzyme also plays a major virulence role during infectivity.

【背景】光滑念珠菌（Candida glabrata）是全球范围内引发念珠菌病的第二大致病菌。与其他酵母菌不同，该菌仅能同化葡萄糖与海藻糖，这一特性被应用于该病原菌的快速鉴定试验；其可向培养基中分泌由CgATH1基因编码的高活性酸性海藻糖酶（acid trehalase）。【目的】本研究旨在解析酸性海藻糖酶在光滑念珠菌病理生理过程中的功能。【方法】通过基因敲除构建ath1Δ突变菌株，验证该突变菌株在海藻糖中的生长能力以及酵母细胞内的海藻糖酶活性；同时利用小鼠感染模型检测ath1Δ菌株的毒力。【结果】ath1Δ突变菌株在葡萄糖环境中生长正常，但丧失了在海藻糖中生长的能力。由于野生型细胞中存在高活性酸性海藻糖酶，仅在ath1Δ突变株中可检测到胞质中性海藻糖酶活性。此外，在正常及免疫功能低下的小鼠感染模型中，ath1Δ菌株的毒力均显著降低。【主要结论】酸性海藻糖酶参与光滑念珠菌对外源海藻糖的水解过程，同时在感染过程中发挥关键的毒力作用。