Kai-Su Pan, Hong Luo, Dong-Yan Zheng, Yan-Qing Zheng, Andrianopoulos Alex, Latgé Jean-Paul, Cun-Wei Cao
Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Guangxi Key Laboratory of Mycosis Research and Prevention, Nanning, China.
Front Microbiol. 2022 Nov 14;13:1033211. doi: 10.3389/fmicb.2022.1033211. eCollection 2022.
() is a thermally dimorphic fungus that can cause opportunistic systemic mycoses. Our previous study demonstrated that concomitant use of berberine (BBR) and fluconazole (FLC) showed a synergistic action against FLC-resistant (B4) . In this paper, we tried to figure out the antifungal mechanisms of BBR and FLC in FLC-resistant. In the microdilution test, the minimum inhibitory concentration (MIC) of FLC was 256 μg/ml before FLC and BBR combination, and was 8 μg/ml after combination, the partial inhibitory concentration index (FICI) of B4 was 0.28. After the treatments of BBR and FLC, the studies revealed that (i) increase reactive oxygen species (ROS), (ii) reduce ergosterol content, (iii) destroy the integrity of cell wall and membrane, (iv) decrease the expression of genes , , , and however and change are not obvious. These results confirmed that BBR has antifungal effect on , and the combination with FLC can restore the susceptibility of FLC-resistant strains to FLC, and the reduction of ergosterol content and the down-regulation of gene expression of , and are the mechanisms of the antifungal effect after the combination, which provides a theoretical basis for the application of BBR in the treatment of Talaromycosis and opens up new ideas for treatment of Talaromycosis.
（某菌）是一种可引起机会性系统性真菌病的热双态真菌。我们之前的研究表明，黄连素（BBR）和氟康唑（FLC）联合使用对耐氟康唑的（B4菌株）具有协同作用。在本文中，我们试图弄清楚BBR和FLC对耐氟康唑菌株的抗真菌机制。在微量稀释试验中，FLC与BBR联合使用前，FLC的最低抑菌浓度（MIC）为256μg/ml，联合使用后为8μg/ml，B4菌株的部分抑菌浓度指数（FICI）为0.28。经过BBR和FLC处理后，研究发现：（i）增加活性氧（ROS）；（ii）降低麦角甾醇含量；（iii）破坏细胞壁和细胞膜的完整性；（iv）降低基因、、、和的表达，然而和的变化不明显。这些结果证实，BBR对（该菌）有抗真菌作用，与FLC联合使用可恢复耐氟康唑菌株对FLC的敏感性，麦角甾醇含量的降低以及、和基因表达的下调是联合使用后抗真菌作用的机制，这为BBR在治疗（某菌病）中的应用提供了理论依据，并为（某菌病）的治疗开辟了新思路。
