Wang Yuchen, Guo Xi, Zhang Xinran, Chen Ping, Wang Wenhui, Hu Shan, Ma Teng, Zhou Xingchen, Li Dongming, Yang Ying
Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, China.
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjing 300457, China.
J Fungi (Basel). 2023 Aug 2;9(8):815. doi: 10.3390/jof9080815.
Ten species strains were isolated from the first known fatal case of rhinofacial and rhino-orbital-cerebral candidiasis. Among them, five strains of complex were isolated during the early stage of hospitalization, while five strains of were isolated in the later stages of the disease. Using whole-genome sequencing, we distinguished the five strains of . complex as four strains and one strain. Antifungal susceptibility testing showed that the five strains of complex were susceptible to all antifungal drugs, while five strains had high minimum inhibitory concentrations to azoles, whereas antifungal-drug resistance gene analysis revealed the causes of azole resistance in such strains. For the first time, we analyzed the microevolutionary characteristics of pathogenic fungi in human hosts and inferred the infection time and parallel evolution of strains. Molecular clock analysis revealed that azole-resistant infection occurred during the first round of therapy, followed by divergence via parallel evolution in vivo. The presence/absence variations indicated a potential decrease in the virulence of genomes in strains isolated following antifungal drug treatment, despite the absence of observed clinical improvement in the conditions of the patient. These results suggest that genomic analysis could serve as an auxiliary tool in guiding clinical diagnosis and treatment.
从首例已知的鼻面部及鼻眶脑型念珠菌病致死病例中分离出10个菌种菌株。其中，5株复合体菌株在住院初期分离得到，而另外5株在疾病后期分离得到。通过全基因组测序，我们将5株复合体菌株区分为4株菌株和1株菌株。药敏试验表明，5株复合体菌株对所有抗真菌药物敏感，而5株菌株对唑类药物的最低抑菌浓度较高，而抗真菌药物耐药基因分析揭示了此类菌株中唑类耐药的原因。我们首次分析了人类宿主中致病真菌的微观进化特征，并推断了菌株的感染时间和平行进化情况。分子钟分析表明，唑类耐药感染发生在第一轮治疗期间，随后在体内通过平行进化发生分化。存在/缺失变异表明，尽管患者病情未观察到临床改善，但抗真菌药物治疗后分离出的菌株基因组毒力可能降低。这些结果表明，基因组分析可作为指导临床诊断和治疗的辅助工具。
