{"title":"对活体进化念珠菌的全基因组分析揭示了多重耐药机制","authors":"Xin-Fei Chen, Han Zhang, Ling-Li Liu, Li-Na Guo, Wen-Jing Liu, Ya-Li Liu, Ding-Ding Li, Ying Zhao, Ren-Yuan Zhu, Yi Li, Rong-Chen Dai, Shu-Ying Yu, Jin Li, Tong Wang, Hong-Tao Dou, Ying-Chun Xu","doi":"10.1007/s11046-024-00832-7","DOIUrl":null,"url":null,"abstract":"<p><i>Candida auris</i>, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in <i>in vivo</i>-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of <i>C. auris</i> using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in <i>ERG11</i> and A585S in <i>TAC1b</i>, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in <i>TAC1</i>b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the <i>SNG1</i> gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of <i>C. auris</i> and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in <i>C. auris</i>.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms\",\"authors\":\"Xin-Fei Chen, Han Zhang, Ling-Li Liu, Li-Na Guo, Wen-Jing Liu, Ya-Li Liu, Ding-Ding Li, Ying Zhao, Ren-Yuan Zhu, Yi Li, Rong-Chen Dai, Shu-Ying Yu, Jin Li, Tong Wang, Hong-Tao Dou, Ying-Chun Xu\",\"doi\":\"10.1007/s11046-024-00832-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><i>Candida auris</i>, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in <i>in vivo</i>-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of <i>C. auris</i> using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in <i>ERG11</i> and A585S in <i>TAC1b</i>, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in <i>TAC1</i>b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the <i>SNG1</i> gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of <i>C. auris</i> and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. 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引用次数: 0
摘要
白色念珠菌(Candida auris)是一种新出现的对多种药物产生耐药性的真菌病原体,已在中国爆发多次疫情。虽然对唑类和两性霉素 B 的耐药机制已有研究,但对该病原体的耐药性发展,尤其是对体内产生的耐药菌株的耐药性发展仍然知之甚少。本研究采用病原体全基因组测序技术,利用从两名患者体内分离出的 16 株菌株,对蛔虫的流行病学和耐药性突变进行了研究。通过基质辅助激光解吸/电离飞行时间质谱进行了鉴定,并使用肉汤微稀释和 Sensititre YeastOne YO10 评估了抗菌药敏感性。全基因组测序显示,所有分离株都属于南亚系,具有遗传异质性。尽管患者分离株之间的基因变异性较低,但还是发现了一些明显的突变,包括 ERG11 中的 Y132F 和 TAC1b 中的 A585S,这可能与氟康唑耐药性增强有关。来自患者 B 的菌株还携带 TAC1b 中的 F214L,导致所有分离株的伏立康唑最低抑菌浓度一致为 4 µg/mL。此外,与易感分离株相比,在对两性霉素 B 耐药的分离株中观察到 SNG1 基因发生了新的框架移位突变。我们的研究结果表明,球孢子菌可能会传播,并强调有必要探索与抗真菌耐药性有关的变异。这就需要分析基因组突变和核型,尤其是体内基因组突变和核型,以比较敏感菌株和耐药菌株。进一步的监测和验证工作对于全面了解蛔虫的抗药性机制至关重要。
Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms
Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.
期刊介绍:
Mycopathologia is an official journal of the International Union of Microbiological Societies (IUMS). Mycopathologia was founded in 1938 with the mission to ‘diffuse the understanding of fungal diseases in man and animals among mycologists’. Many of the milestones discoveries in the field of medical mycology have been communicated through the pages of this journal. Mycopathologia covers a diverse, interdisciplinary range of topics that is unique in breadth and depth. The journal publishes peer-reviewed, original articles highlighting important developments concerning medically important fungi and fungal diseases. The journal highlights important developments in fungal systematics and taxonomy, laboratory diagnosis of fungal infections, antifungal drugs, clinical presentation and treatment, and epidemiology of fungal diseases globally. Timely opinion articles, mini-reviews, and other communications are usually invited at the discretion of the editorial board. Unique case reports highlighting unprecedented progress in the diagnosis and treatment of fungal infections, are published in every issue of the journal. MycopathologiaIMAGE is another regular feature for a brief clinical report of potential interest to a mixed audience of physicians and laboratory scientists. MycopathologiaGENOME is designed for the rapid publication of new genomes of human and animal pathogenic fungi using a checklist-based, standardized format.