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揭示雷帕霉素对该复合物毒力因子的影响。

Revealing the impact of Rapamycin on the virulence factors of the complex.

作者信息

Alves Vinicius, de Andrade Iara Bastos, Corrêa-Junior Dario, Avellar-Moura Igor, Passos Karini, Soares Juliana, Pontes Bruno, Almeida Marcos Abreu, Almeida-Paes Rodrigo, Frases Susana

机构信息

Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Laboratório de Pinças Ópticas, Instituto de Ciências Biomédicas & Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

出版信息

Curr Res Microb Sci. 2024 Jun 7;7:100247. doi: 10.1016/j.crmicr.2024.100247. eCollection 2024.

Abstract

The incidence of invasive fungal infections caused by species is increasing, particularly in immunocompromised individuals. This increasing incidence poses a dual challenge, comprising escalating antifungal resistance and the necessity for accurate fungal identification. The complex further complicates these challenges due to limited identification tools. Like some other species, infections involving this complex show resistance to multiple antifungals, requiring innovative therapeutic approaches. Rapamycin, known for its antifungal properties and immunosuppressive characteristics, was investigated against the complex species. Results revealed a rapamycin minimal inhibitory concentration (MIC) range of 0.07 to >20 µM, with fungicidal effects in most strains. analyses using the rapamycin maximum plasma concentration (0.016 µM) showed reduced surface properties and decreased production of extracellular enzymes. Rapamycin also hindered biofilm formation by some strains. Even when treated at the human therapeutic dose, which is lower than the MIC, phenotypic variations in were detected, hinting at the possible attenuation of some virulence factors when exposed to rapamycin.

摘要

由该菌种引起的侵袭性真菌感染的发病率正在上升,尤其是在免疫功能低下的个体中。这种发病率的上升带来了双重挑战,包括不断增加的抗真菌耐药性以及准确鉴定真菌的必要性。由于鉴定工具有限,该菌种复合体使这些挑战更加复杂。与其他一些菌种一样,涉及该复合体的感染对多种抗真菌药物表现出耐药性,需要创新的治疗方法。雷帕霉素以其抗真菌特性和免疫抑制特性而闻名,被用于研究针对该菌种复合体。结果显示雷帕霉素的最小抑菌浓度(MIC)范围为0.07至>20μM,对大多数菌株具有杀菌作用。使用雷帕霉素最大血浆浓度(0.016μM)进行的分析显示表面特性降低,细胞外酶的产生减少。雷帕霉素还阻碍了一些菌株的生物膜形成。即使在低于MIC的人类治疗剂量下进行治疗,也检测到该菌种的表型变化,这表明在接触雷帕霉素时某些毒力因子可能会减弱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a4f/11225706/2fc2cbced3fb/ga1.jpg

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