Department of Paediatrics, Neonatology, and Paediatric Intensive Care Medicine Academic Hospital, Robert-Koch-Strasse 2D, Itzehoe, Germany.
Med Mycol. 2011 Apr;49 Suppl 1:S96-S100. doi: 10.3109/13693786.2010.502190. Epub 2011 Jan 24.
We discuss in this work the role of Aspergillus biofilms in the clinical setting by reviewing the most recent findings on this topic. Aspergillus fumigatus can produce in vitro an extracellular hydrophobic matrix with typical biofilm characteristics under all static conditions tested, i.e., agar media, polystyrene and bronchial epithelial cells. Under static conditions the mycelial growth is greater than in shaken, submerged conditions. The extracellular matrix (ECM) is composed of galactomannan, α-1,3-glucans, monosaccharides and polyols, melanin and proteins including major antigens and hydrophobins. Typical biofilm structures were observed in the aspergillomas from two patients and in a murine model of invasive pulmonary aspergillosis. The results indicate that α-1,3-glucans plays a predominant role in the agglutination of the hyphae together in aerial conditions, and that nutrient starvation was responsible for mycelial death in aspergilloma. Melanin was produced during the infection, suggesting that this pigment is necessary for lung tissue invasion. All antifungal drugs are significantly less effective when A. fumigatus is grown under biofilm vs. planktonic conditions. Chronic persistence of a unique genotype of A. fumigatus in the respiratory tract of CF-patients and the presence of an ECM in vivo may have some therapeutical application for aspergillosis. The most appropriate antifungal drug should not be selected only on the basis of its efficiency to kill in vitro grown fungal cells, but also on its ability to penetrate the ECM.
我们通过回顾该主题的最新研究结果,讨论了曲霉生物膜在临床环境中的作用。烟曲霉在所有测试的静态条件下,即在琼脂培养基、聚苯乙烯和支气管上皮细胞中,都可以产生具有典型生物膜特征的细胞外疏水性基质。在静态条件下,菌丝体的生长大于在摇瓶、浸没条件下的生长。细胞外基质 (ECM) 由半乳糖甘露聚糖、α-1,3-葡聚糖、单糖和多元醇、黑色素和包括主要抗原和疏水性蛋白在内的蛋白质组成。在两名患者的曲霉肿和侵袭性肺曲霉病的小鼠模型中观察到了典型的生物膜结构。结果表明,α-1,3-葡聚糖在空气中菌丝体聚集中起主要作用,营养饥饿是曲霉肿中菌丝体死亡的原因。黑色素在感染过程中产生,表明这种色素对于肺组织侵袭是必要的。与浮游生物相比,当烟曲霉在生物膜下生长时,所有抗真菌药物的效果都明显降低。在 CF 患者的呼吸道中独特基因型的烟曲霉的慢性持续存在和 ECM 的存在可能对曲霉病具有一定的治疗应用。最适合的抗真菌药物不应仅基于其体外杀死真菌细胞的效率来选择,还应基于其穿透 ECM 的能力。