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马来酰亚胺化合物对 的毒力因子的抑制作用。

Inhibitory effects of a maleimide compound on the virulence factors of .

机构信息

School of Medical Technology, Xuzhou Medical University, Xuzhou, China.

Clinical Laboratory, The Central Hospital of Xuzhou City, Xuzhou, China.

出版信息

Virulence. 2023 Dec;14(1):2230009. doi: 10.1080/21505594.2023.2230009.

Abstract

Candidiasis caused by infection has long been a serious human health problem. The pathogenicity of is mainly due to its virulence factors, which are novel targets of antifungal drugs for low risk of resistance development. In this study, we identified a maleimide compound [1-(4-methoxyphenyl)-1hydro-pyrrole-2,5-dione, MPD] that exerts effective anti-virulence activity. It could inhibit the process of adhesion, filamentation, and biofilm formation in . In addition, it exhibited low cytotoxicity, hemolytic activity, and drug resistance development. Moreover, in () infection model, the survival time of infected larvae was significantly prolonged under the treatment of MPD. Further, mechanism research revealed that MPD increased farnesol secretion by upregulating the expression of Dpp3. The increased farnesol inhibited the activity of Cdc35, which then decreased the intracellular cAMP content resulting in the inhibition of virulence factors via the Ras1-cAMP-Efg1 pathway. In all, this study evaluated the inhibitory effect of MPD on various virulence factors of and identified the underlying mechanisms. This suggests a potential application of MPD to overcome fungal infections in clinics.

摘要

感染引起的念珠菌病一直是一个严重的人类健康问题。的致病性主要是由于其毒力因子,这些毒力因子是抗真菌药物的新型靶标,不易产生耐药性。在这项研究中,我们鉴定了一种马来酰亚胺化合物[1-(4-甲氧基苯基)-1-羟-吡咯-2,5-二酮,MPD],它具有有效的抗毒力活性。它可以抑制的黏附、菌丝形成和生物膜形成过程。此外,它表现出低细胞毒性、溶血活性和耐药性发展。此外,在()感染模型中,MPD 处理后感染幼虫的存活时间显著延长。进一步的机制研究表明,MPD 通过上调 Dpp3 的表达增加法呢醇的分泌。增加的法呢醇抑制了 Cdc35 的活性,从而降低了细胞内 cAMP 含量,通过 Ras1-cAMP-Efg1 途径抑制了毒力因子。总之,本研究评估了 MPD 对的各种毒力因子的抑制作用,并确定了潜在的作用机制。这表明 MPD 有可能在临床上用于克服真菌感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e9/10321171/a252522ba17c/KVIR_A_2230009_F0001_OC.jpg

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