{"title":"从北京血液中分离出的一株南亚支系(I)白色念珠菌的抗药性和毒力基因特征。","authors":"Jing-Xian Yang, Guan-Nan Ma, Ya-Tong Li, Yu-Peng Shi, Guo-Wei Liang","doi":"10.1016/j.clinsp.2024.100497","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing.</p><p><strong>Method: </strong>This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance.</p><p><strong>Results: </strong>Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1.</p><p><strong>Discussion: </strong>The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.</p>","PeriodicalId":10472,"journal":{"name":"Clinics","volume":"79 ","pages":"100497"},"PeriodicalIF":2.2000,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419799/pdf/","citationCount":"0","resultStr":"{\"title\":\"Resistance and virulence genes characteristic of a South Asia Clade (I) Candida auris strain isolated from blood in Beijing.\",\"authors\":\"Jing-Xian Yang, Guan-Nan Ma, Ya-Tong Li, Yu-Peng Shi, Guo-Wei Liang\",\"doi\":\"10.1016/j.clinsp.2024.100497\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing.</p><p><strong>Method: </strong>This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance.</p><p><strong>Results: </strong>Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1.</p><p><strong>Discussion: </strong>The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.</p>\",\"PeriodicalId\":10472,\"journal\":{\"name\":\"Clinics\",\"volume\":\"79 \",\"pages\":\"100497\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419799/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.clinsp.2024.100497\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.clinsp.2024.100497","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
介绍:白色念珠菌是一种全球传播的侵袭性子囊酵母菌,给医疗保健系统带来了沉重负担。据记载,它已传播到六大洲的 40 多个国家,因此有必要通过全基因组测序等先进技术对其进行深入了解:本研究从北京一名患者的血液中分离出一株对氟康唑耐药的阿氏杆菌(CA01),并对其进行了全基因组测序。通过基因组分析对菌株进行分类,并进行分子对接以了解突变对耐药性的影响:基因组分析表明,CA01属于南亚支系(I),与之前报道的菌株BJCA001和BJCA002有着最密切的遗传关系。值得注意的是,与 BJCA001 不同,CA01 对氟康唑表现出明显的耐药性,主要是由于 ERG11 基因中的 A395T 突变。分子对接研究表明,这种突变导致氟康唑结合的活性位点发生几何变化,从而降低了结合亲和力。此外,本研究结果还发现了 C. auris 的几个核心毒力基因,如 RBF1:本研究的发现拓展了对南亚支系(I)中 C. auris 遗传多样性和适应机制的认识。观察到的由ERG11突变A395T驱动的氟康唑耐药性凸显了在中国临床治疗策略中提高意识和适应性的必要性。这项研究从基因水平上提供了耐药性和毒力特征的重要见解,可指导未来对蛔虫感染的治疗和管理策略。
Resistance and virulence genes characteristic of a South Asia Clade (I) Candida auris strain isolated from blood in Beijing.
Introduction: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing.
Method: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance.
Results: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1.
Discussion: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.
期刊介绍:
CLINICS is an electronic journal that publishes peer-reviewed articles in continuous flow, of interest to clinicians and researchers in the medical sciences. CLINICS complies with the policies of funding agencies which request or require deposition of the published articles that they fund into publicly available databases. CLINICS supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration.