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基质辅助激光解吸电离飞行时间质谱技术在检测人类病原体光滑念珠菌中抗真菌药物耐药性的潜在应用

Potential Use of MALDI-ToF Mass Spectrometry for Rapid Detection of Antifungal Resistance in the Human Pathogen Candida glabrata.

机构信息

Institute of Microbiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo F. Vito 1, 00168, Rome, Italy.

Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey, 07103, USA.

出版信息

Sci Rep. 2017 Aug 22;7(1):9099. doi: 10.1038/s41598-017-09329-4.

Abstract

The echinocandins are relatively new antifungal drugs that represent, together with the older azoles, the recommended and/or preferred agents to treat candidaemia and other forms of invasive candidiasis in human patients. If "time is of the essence" to reduce the mortality for these infections, the administration of appropriate antifungal therapy could be accelerated by the timely reporting of laboratory test results. In this study, we attempted to validate a MALDI-ToF mass spectrometry-based assay for the antifungal susceptibility testing (AFST) of the potentially multidrug-resistant pathogen Candida glabrata against anidulafungin and fluconazole. The practical applicability of the assay, reported here as MS-AFST, was assessed with a panel of clinical isolates that were selected to represent phenotypically and genotypically/molecularly susceptible or resistant strains. The data show the potential of our assay for rapid detection of antifungal resistance, although the MS-AFST assay performed at 3 h of the in vitro antifungal exposure failed to detect C. glabrata isolates with echinocandin resistance-associated FKS2 mutations. However, cell growth kinetics in the presence of anidulafungin revealed important cues about the in vitro fitness of C. glabrata isolates, which may lead to genotypic or phenotypic antifungal testing in clinical practice.

摘要

棘白菌素类是相对较新的抗真菌药物,与较老的唑类药物一起,是治疗人类患者念珠菌血症和其他侵袭性念珠菌病的推荐和/或首选药物。如果“时间至关重要”,要降低这些感染的死亡率,可以通过及时报告实验室检测结果来加速适当的抗真菌治疗。在这项研究中,我们试图验证一种基于 MALDI-ToF 质谱的抗真菌药敏试验(AFST),用于检测潜在多药耐药病原体光滑念珠菌对安尼拉芬净和氟康唑的药敏性。这里报告的 MS-AFST 评估了该检测方法的实际适用性,使用了一组临床分离株,这些分离株代表表型和基因型/分子敏感或耐药菌株。数据显示,我们的检测方法具有快速检测抗真菌耐药性的潜力,尽管在体外抗真菌暴露 3 小时进行的 MS-AFST 检测未能检测到具有棘白菌素耐药相关 FKS2 突变的光滑念珠菌分离株。然而,在安尼拉芬净存在下的细胞生长动力学揭示了关于光滑念珠菌分离株体外适应性的重要线索,这可能导致在临床实践中进行基因型或表型抗真菌检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91a3/5567316/e7efea2aad17/41598_2017_9329_Fig1_HTML.jpg

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