Department of Dermatology, PLA Army General Hospital, 5 Nanmencang, Dongcheng District, Beijing, 100700, China.
Graduate School, Third Military Medical University, Chongqing, China.
Mycopathologia. 2017 Oct;182(9-10):829-837. doi: 10.1007/s11046-017-0119-7. Epub 2017 Jan 31.
Trichosporon asahii (T. asahii) is an opportunistic pathogen that can cause life-threatening infections in immunocompromised patients, with high mortality rates up to 80% despite treated with antifungal drugs. The biofilms-forming ability of T. asahii on indwelling medical devices may account for the resistance to antifungal drugs. Berberine (BBR) has been demonstrated to have antifungal activity and synergistic effects in combination with antifungal drugs against pathogenic fungi. In the present study, the in vitro activities of BBR alone or combined with fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), caspofungin (CAS) and amphotericin B (AMB) against planktonic forms and biofilms of 21 clinical T. asahii isolates were evaluated using checkerboard microdilution method and XTT reduction assay, respectively. The fractional inhibitory concentration index (FICI) was used to interpret drug interactions. BBR alone did not exhibit significant antifungal activities against both T. asahii planktonic cells (MICs, 32 → 128 μg/ml) and T. asahii biofilms (SMICs, >128 μg/ml). However, BBR exhibited synergistic effects against T. asahii planktonic cells in combination with AMB, FLC and CAS (FICI ≤ 0.5) and exhibited synergistic effects against T. asahii biofilms in combination with AMB and CAS (FICI ≤ 0.5). BBR/ITC and BBR/VRC combinations yielded mainly indifferent interactions against T. asahii planktonic cells. BBR/FLC, BBR/ITC and BBR/VRC combinations also yielded indifferent interactions against T. asahii biofilms. Our study highlights the therapeutic potential of BBR to be used as an antifungal synergist in combination with antifungal drugs against T. asahii infections, especially BBR/AMB combination. Further in vivo studies are needed to validate our findings.
近平滑念珠菌（T. asahii）是一种机会性病原体，可在免疫功能低下的患者中引起危及生命的感染，尽管用抗真菌药物治疗，但其死亡率仍高达 80%。T. asahii 在留置医疗器械上形成生物膜的能力可能是其对抗真菌药物产生耐药性的原因。黄连素（BBR）已被证明具有抗真菌活性，并与抗真菌药物联合使用时对致病性真菌具有协同作用。在本研究中，采用棋盘微量稀释法和 XTT 还原试验分别评估了 BBR 单独或与氟康唑（FLC）、伊曲康唑（ITC）、伏立康唑（VRC）、卡泊芬净（CAS）和两性霉素 B（AMB）联合应用对 21 株临床近平滑念珠菌分离株浮游形式和生物膜的体外活性。采用部分抑菌浓度指数（FICI）来解释药物相互作用。BBR 单独对 T. asahii 浮游细胞（MICs，32→128μg/ml）和 T. asahii 生物膜（SMICs，>128μg/ml）均无显著抗真菌活性。然而，BBR 与 AMB、FLC 和 CAS 联合应用时对 T. asahii 浮游细胞表现出协同作用（FICI≤0.5），与 AMB 和 CAS 联合应用时对 T. asahii 生物膜表现出协同作用（FICI≤0.5）。BBR/ITC 和 BBR/VRC 联合用药对 T. asahii 浮游细胞主要表现为无关相互作用。BBR/FLC、BBR/ITC 和 BBR/VRC 联合用药对 T. asahii 生物膜也表现出无关相互作用。本研究强调了 BBR 作为抗真菌增效剂与抗真菌药物联合应用治疗 T. asahii 感染的治疗潜力，尤其是 BBR/AMB 联合用药。需要进一步的体内研究来验证我们的发现。
