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新型噻唑啉基-吡啶甲酰胺基钯(II)配合物减轻导致阴道念珠菌病 (VVC) 的念珠菌的毒力和生物膜。

Novel thiazolinyl-picolinamide-based palladium(II) complex extenuates the virulence and biofilms of vulvovaginal candidiasis (VVC) causing Candida.

机构信息

Biofilm Biology Laboratory, Centre for Research on Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, 613401, India.

Organometallics and Catalysis Laboratory, Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, 613401, India.

出版信息

Int Microbiol. 2024 Oct;27(5):1527-1539. doi: 10.1007/s10123-024-00497-8. Epub 2024 Mar 11.

Abstract

Candida infections are growing all over the world as a result of their resistance to anti-fungal drugs. This raises concerns about public health, particularly in cases of vulvovaginal candidiasis (VVC). Therefore, the need for effective treatment options for Candida infections has become crucial. The main goal of the study is to evaluate the efficacy of novel palladium metal complexes against fluconazole-resistant Candida spp., particularly C. albicans and C. auris. The process begins with identifying the minimum inhibitory concentration (MIC), followed by growth curve assays, colony morphology analysis, characterization, and gene expression analysis. The investigation revealed that sub-MIC of Pd(II) complex B (250 μg/mL) inhibited Candida spp. more effectively than amphotericin B (500 μg/mL). Further, Pd(II) complex B drastically reduced the growth of Candida spp. biofilms by 70-80% for nascent biofilms and 70-75% for mature biofilms. Additionally, the yeast-to-hyphal switch and SEM studies revealed that Pd(II) complex B effectively hinders the growth of drug-resistant Candida cells. The gene expression investigation also evidenced that Pd(II) complex B downregulated virulence genes in C. albicans (ERG, EFG, UME6, and HGC) and C. auris (ERG, CDR, and HGC). The findings showed that Pd(II) complex B effectively inhibited the growth of Candida biofilm formation and was reported as a potential anti-biofilm agent against Candida spp. that are resistant to drugs.

摘要

由于抗真菌药物的耐药性,世界各地的念珠菌感染呈上升趋势。这引起了人们对公共卫生的关注,尤其是在阴道念珠菌病(VVC)的情况下。因此,对于念珠菌感染的有效治疗选择变得至关重要。本研究的主要目的是评估新型钯金属配合物对氟康唑耐药念珠菌属(尤其是白色念珠菌和耳念珠菌)的疗效。该过程从确定最小抑菌浓度(MIC)开始,然后进行生长曲线测定、菌落形态分析、表征和基因表达分析。研究表明,亚 MIC 的 Pd(II) 配合物 B(250 μg/mL)比两性霉素 B(500 μg/mL)更有效地抑制念珠菌属。此外,Pd(II) 配合物 B 可使新生生物膜和成熟生物膜的生物膜生长分别减少 70-80%和 70-75%。此外,酵母到菌丝的转变和 SEM 研究表明,Pd(II) 配合物 B 有效地抑制了耐药念珠菌细胞的生长。基因表达研究还表明,Pd(II) 配合物 B 下调了白色念珠菌(ERG、EFG、UME6 和 HGC)和耳念珠菌(ERG、CDR 和 HGC)中的毒力基因。研究结果表明,Pd(II) 配合物 B 可有效抑制念珠菌生物膜形成的生长,被报道为一种针对耐药念珠菌属的潜在抗生物膜剂。

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