左旋多巴对马尔尼菲青霉黑素合成以及药敏的影响

目的 探讨左旋多巴对马尔尼菲青霉黑素合成的影响及黑素化是否影响马尔尼菲青霉对抗真菌药的敏感性。 方法 将马尔尼菲青霉临床分离株GXMU121011分别接种于沙氏葡萄糖琼脂培养基37 ℃培养7 d，观察左旋多巴不同浓度（0.1 ~ 10.0 mmol/L）和马尔尼菲青霉不同接种密度（1.0 × 105 ~ 1.0 × 107 cfu/ml）对马尔尼菲青霉黑素生成的影响。用纸片法进行体外抗真菌药敏试验，分别测定伊曲康唑、氟康唑和两性霉素B对8株马尔尼菲青霉菌株在含左旋多巴和不含左旋多巴培养时的抑菌圈大小。 结果 左旋多巴浓度由0.1 mmol/L增加至1.0 mmol/L时，马尔尼菲青霉菌落变黑程度随之增加；左旋多巴浓度处在1.0 mmol/L或3.0 mmol/L时，菌落最黑，左旋多巴浓度继续增加时菌落黑化程度减轻，左旋多巴浓度在10.0 mmol/L时菌体出现轻微皱缩的现象。菌落颜色随着接种菌密度的逐渐升高而加深。伊曲康唑、两性霉素B和氟康唑对含左旋多巴培养的马尔尼菲青霉抑菌圈平均直径均显著小于不含左旋多巴培养的马尔尼菲青霉（P < 0.05）。 结论 左旋多巴的浓度和接种菌落的密度影响马尔尼菲青霉黑素的生成。黑素化培养可以降低酵母相马尔尼菲青霉对伊曲康唑、氟康唑和两性霉素B的敏感性。

Effect of levodopa on melanogenesis in and antifungal drug susceptibility of Penicillium marneffei

Peng Cheng, Sun Xian, Liu Donghua. Department of Dermatology and Venereology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China Corresponding author: Liu Donghua, Email: ldhgxmu@163.com 【Abstract】 Objective To investigate the effect of levodopa on melanogenesis in Penicillium marneffei （PM）, and to determine if melanization affects the antifungal drug susceptibility of PM. Methods A clinical isolate of PM, GXMU121011, was inoculated onto Sabouraud′s dextrose agar （SDA） containing different concentrations （0.1 - 10 mmol/L） of levodopa at an inoculum density of 1.0 × 106 cfu/ml, or onto SDA containing 1 mmol/L levodopa at three inoculum densities （1.0 × 105, 1.0 × 106, 1.0 × 107 cfu/ml）, and cultured at 37 ℃ for 7 days. Subsequently, melanization of PM colonies was observed. The paper-disk method was used for antifungal susceptibility testing, and the diameter of inhibition zones of itraconazole, fluconazole and amphotericin B against 8 clinical strains of PM was determined on SDA with or without levodopa. Results The melanization of PM colonies increased when the concentration of levodopa increased from 0.1 to 1.0 mmol/L, peaked when that reached 1.0 and 3.0 mmol/L, but mildly decreased when that continuously increased beyond 3.0 mmol/L, and a slight shrinkage was observed in PM colonies when that was 10.0 mmol/L. The color of colonies deepened along with the increase in inoculum density of PM. The average diameters of inhibition zones of itraconazole, fluconazole and amphotericin B against PM were all significantly lower on SDA with levodopa than on SDA without levodopa （all P < 0.05）. Conclusions Levodopa concentration and inoculum density both affect melanogenesis in PM. Melanization may decrease the susceptibility of PM in yeast phase to itraconazole, fluconazole and amphotericin B in vitro.