Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-09-12 DOI:10.1038/s41368-023-00245-0
Xiaoyue Liang, Ding Chen, Jiannan Wang, Binyou Liao, Jiawei Shen, Xingchen Ye, Zheng Wang, Chengguang Zhu, Lichen Gou, Xinxuan Zhou, Lei Cheng, Biao Ren, Xuedong Zhou
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Abstract

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

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青蒿素通过抑制白念珠菌菌丝的发育来抑制口腔念珠菌病。
白色念珠菌是口腔中最丰富的真菌种类。作为一种聪明的机会致病菌,它通过从酵母菌到菌丝的转变来增加毒力,成为口腔念珠菌病的主要致病菌。然而,目前临床抗真菌药物的过度使用和新型药物的缺乏突出了抗真菌治疗的挑战,因为它的耐药性和副作用。抗毒策略已被证明是开发新型抗感染药物的可行途径。本研究利用青蒿素、双氢青蒿素、青蒿酸、双氢青蒿酸、青蒿琥酯、蒿醚和蒿醚等7种青蒿素靶向白色念珠菌最重要的毒力因子菌丝发育。青蒿素对白色念珠菌(包括临床抗唑菌株)的生长没有影响,但能显著抑制菌丝发育,降低其对口腔上皮细胞的损伤,其中青蒿素的作用最强。转录组分析表明,青蒿素可能影响白色念珠菌的能量代谢。结果表明,7种青蒿素均能显著抑制ATP和cAMP的产生,同时降低了RAS1过表达菌株对菌丝的抑制作用,表明青蒿素通过调控RAS1 -cAMP- efg1通路抑制菌丝的发育。重要的是,青蒿醚显著抑制氟康唑敏感和耐药菌株引起的小鼠口咽念珠菌病模型体内真菌负荷和感染,无全身毒性。我们的研究结果首次表明,青蒿素可能是潜在的抗白色念珠菌感染的化合物,其目标是其菌丝的发育。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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