Baillie G S, Douglas L J
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Antimicrob Agents Chemother. 1998 Aug;42(8):1900-5. doi: 10.1128/AAC.42.8.1900.
A perfused biofilm fermentor, which allows growth-rate control of adherent microbial populations, was used to assess whether the susceptibility of Candida albicans biofilms to antifungal agents is dependent on growth rate. Biofilms were generated under conditions of glucose limitation and were perfused with drugs at a high concentration (20 times the MIC). Amphotericin B produced a greater reduction in the number of daughter cells in biofilm eluates than ketoconazole, fluconazole, or flucytosine. Similar decreases in daughter cell counts were observed when biofilms growing at three different rates were perfused with amphotericin B. In a separate series of experiments, intact biofilms, resuspended biofilm cells, and newly formed daughter cells were removed from the fermentor and were exposed to a lower concentration of amphotericin B for 1 h. The susceptibility profiles over a range of growth rates were then compared with those obtained for planktonic cells grown at the same rates under glucose limitation in a chemostat. Intact biofilms were resistant to amphotericin B at all growth rates tested, whereas planktonic cells were resistant only at low growth rates (</=0.13 h-1). Cells resuspended from biofilms were less resistant than intact biofilm populations but more resistant than daughter cells; the susceptibilities of both these cell types were largely independent of growth rate. Our findings indicate that the amphotericin B resistance of C. albicans biofilms is not simply due to a low growth rate but depends on some other feature of the biofilm mode of growth.
一种灌注式生物膜发酵罐可控制附着微生物群体的生长速率，利用该发酵罐评估白色念珠菌生物膜对抗真菌剂的敏感性是否取决于生长速率。生物膜在葡萄糖受限的条件下形成，并用高浓度（最低抑菌浓度的20倍）的药物进行灌注。两性霉素B比酮康唑、氟康唑或氟胞嘧啶能使生物膜洗脱液中子代细胞数量减少得更多。当以三种不同速率生长的生物膜用两性霉素B灌注时，观察到子代细胞数量有类似的减少。在另一系列实验中，将完整生物膜、重悬的生物膜细胞和新形成的子代细胞从发酵罐中取出，并用较低浓度的两性霉素B处理1小时。然后将一系列生长速率下的敏感性谱与在恒化器中葡萄糖受限条件下以相同速率生长的浮游细胞所获得的敏感性谱进行比较。在所有测试的生长速率下，完整生物膜对两性霉素B均有抗性，而浮游细胞仅在低生长速率（≤0.13 h⁻¹）时具有抗性。从生物膜中重悬的细胞抗性低于完整生物膜群体，但高于子代细胞；这两种细胞类型的敏感性在很大程度上与生长速率无关。我们的研究结果表明，白色念珠菌生物膜对两性霉素B的抗性并非仅仅由于生长速率低，而是取决于生物膜生长模式的其他特征。
