Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, Jiangsu, China; School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing 211816, Jiangsu, China.
Key Laboratory for Organic Electronics & Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, Jiangsu, China.
Biomed Environ Sci. 2019 Mar;32(3):199-209. doi: 10.3967/bes2019.027.
To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo.
Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).
BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis.
The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.
评估伯克霍尔德氏信号分子顺-2-十二烯酸（BDSF）与氟康唑（FLU）或伊曲康唑（ITRA）联合应用对体外和体内两种唑类耐药白色念珠菌临床分离株的协同作用。
采用棋盘微量稀释法、E 试验和时间杀伤试验测定抗生素对两种唑类耐药白色念珠菌的最低抑菌浓度（MIC）。在小鼠体内进行抗真菌协同试验。通过定量逆转录聚合酶链反应（qRT-PCR）分析菌株的相对基因表达水平。
BDSF 与 FLU 或 ITRA 联合具有高度协同作用，其部分抑菌浓度指数 ⪕ 0.08。BDSF 在高达 300μg/mL 的浓度下对正常人包皮成纤维细胞无细胞毒性。qRT-PCR 结果表明，与单独使用 FLU 或 ITRA 相比，BDSF 与 FLU/ITRA 的联合使用通过分别抑制转录因子 TAC1 和 MRR1 显著抑制外排泵基因 CDR1 和 MDR1 的表达。未发现 ERG1、ERG11 和 UPC2 的 mRNA 表达水平有明显差异，这表明药物联合使用不会显著干扰 UPC2 介导的麦角固醇水平。体内实验表明，联合治疗可能是治疗念珠菌病的有效治疗方法。
BDSF 与唑类药物的协同作用可能是控制唑类耐药念珠菌感染的一种有效方法。
