Data underlying the research of Immunological fitness of echinocandin-resistant Nakaseomyces glabratus

We here described the immunological fitness of echinocandin-resistant Candida glabrata and the consequence in term of management of candidemia. We used different in vitro model (simple and complex) and multiple microscopical techniques. <em>Nakaseomyces glabratus</em> (formerly <em>Candida glabrata</em>) (<em>N. glabratus</em>) is a commensal yeast that is increasingly associated with invasive candidiasis. The rapid acquisition of echinocandin resistance by <em>N. glabratus </em>has raised public health concerns and led the WHO to classify it as a high-priority fungal pathogen in 2022. However, the impact of antifungal resistance on the host immune response remains poorly understood. Since echinocandin resistance often involves alterations to the fungal cell wall, which is critical for host immune recognition, such mutations may affect fungal fitness and immune evasion. We analyzed the immunological fitness of echinocandin-resistant <em>N. glabratus</em> using clinical isolates from a patient with recurrent bloodstream infections. <em>In vitro</em> yeast-macrophage and yeast-human leukocyte co-culture models were used to evaluate immune responses. Echinocandin-resistant isolates exhibited modified cell wall composition. Compared to susceptible strains, the resistant isolates induced a delayed and reduced pro-inflammatory cytokine response and demonstrated prolonged survival within immune aggregates. These findings suggest that immune evasion and persistence may confer additional fitness advantages to echinocandin-resistant <em>N. glabratus</em>, potentially impacting the pathophysiological interactions between host and pathogen

本研究阐明了棘白菌素（echinocandin）耐药光滑假丝酵母菌（*Candida glabrata*）的免疫适应性，及其在念珠菌血症诊疗中的相关影响。本研究采用多种体外（*In vitro*）模型（包括简单与复杂模型）及多种显微技术开展实验。光滑纳塞酵母（*Nakaseomyces glabratus*，原分类为光滑假丝酵母菌*Candida glabrata*，下称*N. glabratus*）是一种共生酵母菌，其与侵袭性念珠菌病的关联日益密切。该菌快速获得棘白菌素耐药性的现象已引发公共卫生领域的广泛关注，世界卫生组织（WHO）于2022年将其列为高优先级真菌病原体。然而，抗真菌耐药性对宿主免疫应答的影响仍有待深入阐明。由于棘白菌素耐药性通常伴随真菌细胞壁的结构改变，而细胞壁是宿主免疫识别的关键靶点，此类耐药突变可能会影响真菌的适应性及免疫逃逸能力。本研究从一名复发性血流感染患者的临床分离株中获取棘白菌素耐药光滑纳塞酵母，对其免疫适应性展开分析。本研究采用体外酵母菌-巨噬细胞共培养模型与酵母菌-人类白细胞共培养模型，对免疫应答进行评估。棘白菌素耐药分离株的细胞壁组成发生了改变。与敏感菌株相比，耐药分离株诱导的促炎细胞因子应答出现延迟且强度降低，同时在免疫聚集体中的存活时间更长。上述研究结果表明，免疫逃逸与持续定植能力可赋予棘白菌素耐药光滑纳塞酵母额外的适应性优势，或可影响宿主与病原体之间的病理生理相互作用。