Department of Molecular and Applied Microbiology, Hans-Knöll-Institute, Jena, Germany.
Proteomics. 2010 Sep;10(17):3097-107. doi: 10.1002/pmic.201000129.
The opportunistic pathogenic mold Aspergillus fumigatus is an increasing cause of morbidity and mortality in immunocompromised and in part immunocompetent patients. A. fumigatus can grow in multicellular communities by the formation of a hyphal network encased in an extracellular matrix. Here, we describe the proteome and transcriptome of planktonic- and biofilm-grown A. fumigatus mycelium after 24 and 48 h. A biofilm- and time-dependent regulation of many proteins and genes of the primary metabolism indicates a developmental stage of the young biofilm at 24 h, which demands energy. At a matured biofilm phase, metabolic activity seems to be reduced. However, genes, which code for hydrophobins, and proteins involved in the biosynthesis of secondary metabolites were significantly upregulated. In particular, proteins of the gliotoxin secondary metabolite gene cluster were induced in biofilm cultures. This was confirmed by real-time PCR and by detection of this immunologically active mycotoxin in culture supernatants using HPLC analysis. The enhanced production of gliotoxin by in vitro formed biofilms reported here may also play a significant role under in vivo conditions. It may confer A. fumigatus protection from the host immune system and also enable its survival and persistence in chronic lung infections such as aspergilloma.
机会致病霉菌烟曲霉是免疫功能低下和部分免疫功能正常患者发病率和死亡率增加的原因。烟曲霉可以通过形成菌丝网络并包裹在细胞外基质中，在多细胞群落中生长。在这里，我们描述了浮游和生物膜培养的烟曲霉菌丝体在 24 和 48 小时后的蛋白质组和转录组。生物膜和时间依赖性调节许多蛋白质和初级代谢物的基因表明，在 24 小时时，年轻生物膜处于需要能量的发育阶段。在成熟的生物膜阶段，代谢活性似乎降低。然而，编码疏水性蛋白和参与次生代谢物生物合成的基因显著上调。特别是，次生代谢物Gliotoxin 基因簇的蛋白在生物膜培养物中被诱导。这通过实时 PCR 和使用 HPLC 分析在培养上清液中检测到这种免疫活性霉菌毒素得到了证实。这里报道的体外形成的生物膜中Gliotoxin 的产量增加，也可能在体内条件下发挥重要作用。它可以使烟曲霉免受宿主免疫系统的侵害，也使其能够在曲霉瘤等慢性肺部感染中存活和持续存在。
