Biomarkers of caspofungin resistance in Candida albicans isolates: A proteomic approach.

Biomarkers of caspofungin resistance in Candida albicans isolates: A proteomic approach.
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DOI:
10.1080/21505594.2022.2081291
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发表时间:
2022-12
期刊:
影响因子:
5.2
通讯作者:
Munro, Carol A.
Munro, Carol A.
中科院分区:
生物学2区
文献类型:
--
作者:
De Cesare, Giuseppe Buda;Hafez, Ahmed;Stead, David;Llorens, Carlos;Munro, Carol A.

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白色念珠菌是临床上重要的多态真菌病原体,可引起危及生命的侵袭性感染免疫功能低下的患者。由于越来越多的耐药菌株的出现,抗真菌治疗失败是一个重大的临床问题。Caspofungin是一种常见的抗真菌药物,常用于一线治疗,抑制细胞壁β-(1,3)-葡聚糖合成。本研究比较了不同棘球白素耐药菌株与敏感菌株的细胞表面,并分析了它们对棘球白素的反应。蛋白质组学分析发现,与敏感菌株相比,耐药菌株和用caspofungin孵育后,参与细胞壁组织和维持的蛋白质库发生了变化。并根据差分表达式的结果建立了交互网络。我们的研究结果表明,耐药性可能不仅涉及不同的细胞壁结构,还涉及对药物的不同反应。
Candida albicans is a clinically important polymorphic fungal pathogen that causes life-threatening invasive infections in immunocompromised patients. Antifungal therapy failure is a substantial clinical problem, due to the emergence of an increasing number of drug-resistant isolates. Caspofungin is a common antifungal drug, often used as first-line therapy that inhibits cell wall β-(1,3)-glucan synthesis. In this work, the cell surface of different echinocandin-resistant C. albicans clinical isolates was compared with sensitive isolates and their responses to echinocandin treatment analyzed. Proteomic analysis detected changes in the repertoire of proteins involved in cell wall organization and maintenance, in drug-resistant strains compared to susceptible isolates and after incubation with caspofungin. Moreover, an interaction network was created from the differential expression results. Our findings suggest drug resistance may involve not only a different cell wall architecture, but also a different response to drugs.
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