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深入了解耳念珠菌的分散细胞及其对抗真菌耐药性的影响。

Insights into Candida auris dispersal cells and their impact on antifungal resistance.

作者信息

Fayed Bahgat

机构信息

Department of Chemistry of Natural and Microbial Products, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Bohouth Street, P.O. 12622, Dokki, Giza, Egypt.

出版信息

BMC Microbiol. 2025 May 29;25(1):342. doi: 10.1186/s12866-025-04055-8.

Abstract

The emerging Candidozyma auris (formerly known as Candida auris, C. auris) has caused several outbreaks globally. While several studies explored the resistant biofilm formed by C. auris, little is known regarding the cells dispersed following biofilm formation. Herein, I investigated and characterized the cells dispersed from C. auris biofilms. Cells dispersed from biofilm developed in 96 well plate were isolated and counted. The antifungal susceptibility testing showed that the dispersed cells display similar antifungal susceptibility as the parent planktonic cells, except amphotericin B. Gene expression analysis performed by quantitative real-time PCR indicated that dispersed cells can express genes coded for antifungal resistance (ERG2, ERG6, ERG11, FKS1, CHS1, CHS2, CDR1, MDR1) more than the parent planktonic cells. It was observed that dispersed cells can acquire resistance to caspofungin faster than the parent planktonic cells once exposed to caspofungin at sub MIC level. Furthermore, biofilms formed by dispersed cells displayed significantly higher metabolic activity, as indicated by the XTT analysis. To provide more insight, I explored the expression of genes coding for biofilm initiation and maturation and the data obtained indicated that dispersed cells overexpressed ALS5 and KRE6 genes. Further, GC-MS analysis indicated that dispersed cells exhibit altered metabolic profile that enhance cells survivability under stress and nutrient limit condition. The presented study is the first to explore C. auris dispersed cells and indicated that they are not able to revert to the planktonic mode once released from the biofilm.

摘要

新兴的耳念珠菌(以前称为耳假丝酵母菌,C. auris)已在全球引发了多起疫情。虽然有几项研究探讨了耳念珠菌形成的耐药生物膜,但对于生物膜形成后分散的细胞却知之甚少。在此,我对从耳念珠菌生物膜中分散出来的细胞进行了研究和表征。分离并计数了在96孔板中形成的生物膜所分散出的细胞。抗真菌药敏试验表明,除两性霉素B外,分散细胞显示出与亲代浮游细胞相似的抗真菌药敏性。通过定量实时PCR进行的基因表达分析表明,分散细胞比亲代浮游细胞能更多地表达编码抗真菌耐药性的基因(ERG2、ERG6、ERG11、FKS1、CHS1、CHS2、CDR1、MDR1)。观察到,一旦在亚抑菌浓度水平下接触卡泊芬净,分散细胞比亲代浮游细胞能更快地获得对卡泊芬净的耐药性。此外,XTT分析表明,由分散细胞形成的生物膜显示出显著更高的代谢活性。为了提供更多见解,我探究了编码生物膜起始和成熟的基因的表达,所获得的数据表明分散细胞过度表达了ALS5和KRE6基因。此外,气相色谱 - 质谱分析表明,分散细胞表现出改变的代谢谱,这增强了细胞在应激和营养限制条件下的生存能力。本研究首次探索了耳念珠菌分散细胞,并表明它们一旦从生物膜中释放出来就无法恢复到浮游模式。

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