Table_1_The first rare case of Candida palmioleophila infection reported in China and its genomic evolution in a human host environment.DOCX

IntroductionCandida palmioleophila is a rare human pathogenic fungus, which has been poorly characterized at the genome level. In this study, we reported the first fatal case of C. palmioleophila infection in China and investigate the microevolution of C. palmioleophila in the human host environment.
MethodsA series of C. palmioleophila stains were collected from the patient at different time points for routine microbial and drug sensitivity testing. The first C. palmioleophila isolate 07202534 was identified by de novo whole genome sequencing. The in vitro and in vivo genetic evolutionary characteristics of C. palmioleophila were discussed based on the analysis of bioinformatics data.
ResultsThe six C. palmioleophila isolates displayed dose-dependent sensitivity to fluconazole. The C. palmioleophila genome contained homologous genes such as CDR1 and MDR1, which were recognized to be related to azole resistance. In addition, amino acid variation was detected at F105L and other important sites of ERG11. In addition, the mean divergence time between C. palmioleophila and Scheffersomyces stipites CBS 6054 was 406.04 million years, indicating that C. palmioleophila originated earlier than its closest relative. In addition, the six strains of C. palmioleophila isolated form the patient had higher homology and fewer mutation sites, which indicated the stability in C. palmioleophila genome. We also found that C. palmioleophila had a wide natural niche and may evolve slowly.
DiscussionWe believe that this study will contribute to improve our understanding of the genetic evolution, pathogenicity, and drug resistance of C. palmioleophila and will aid in the prevention and control of its spread.

引言
棕榈假丝酵母（Candida palmioleophila）是一种罕见的人类致病真菌，其基因组层面的研究尚不完善。本研究报道了国内首例棕榈假丝酵母致死感染病例，并探究了该菌在人类宿主环境中的微进化过程。

材料与方法
从患者不同时间点采集多株棕榈假丝酵母，用于常规微生物学检测与药物敏感性试验。首株分离菌株07202534通过从头全基因组测序完成鉴定。基于生物信息学数据分析，探讨了棕榈假丝酵母的体外与体内遗传进化特征。

结果
6株棕榈假丝酵母分离株对氟康唑呈现剂量依赖性敏感性。该菌基因组中存在CDR1、MDR1等与唑类耐药相关的同源基因。此外，在ERG11基因的F105L等关键位点检测到氨基酸变异。棕榈假丝酵母与施氏假丝酵母（Scheffersomyces stipitis）CBS 6054的平均分歧时间为4.0604亿年，提示其起源早于近缘物种。从同一患者分离的6株棕榈假丝酵母同源性较高且突变位点较少，表明该菌基因组具有稳定性。本研究还发现，棕榈假丝酵母拥有广泛的自然生态位，且进化速率较为缓慢。

讨论
本研究有助于加深对棕榈假丝酵母遗传进化、致病性与耐药性的认识，可为其传播防控工作提供参考依据。