Aspergillus Biofilm In Vitro and In Vivo
Aspergillus Biofilm In Vitro and In Vivo
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DOI：
10.1128/microbiolspec.mb-0017-2015
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发表时间：
2015-08-01
影响因子：
3.7
通讯作者：
Latge, Jean-Paul
中科院分区：
文献类型：
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作者：
Beauvais, Anne;Latge, Jean-Paul
在体内，烟曲霉以典型的生物膜形式生长，菌丝被由多糖、半乳甘露聚糖和半乳糖氨基半乳糖组成的细胞外基质(ECM)覆盖。α-1，3-葡聚糖和黑色素也是曲菌球细胞外基质的组成成分，但在侵袭性曲霉病中不是。在体外，建立了两个模拟体内情况的生物膜模型。第一种模式(模式1)采用液体沉水条件，具有生长缓慢的特点，而第二种模式(模式2)采用琼脂培养和气生条件，具有快速生长的特点。仅在第二个模型中研究了ECM的组成，并已证明其由半乳甘露聚糖、半乳糖氨基半乳糖(GAG)、a1，3葡聚糖、黑色素、抗原和疏水素组成。在模型1生物膜中检测到胞外DNA的存在，但在模型2中未检测到。采用两种生物膜模型的转录分析显示，参与次生代谢物生物合成、黏附和耐药性的蛋白质编码基因上调。然而，大多数关于烟曲霉菌生物膜的数据都是在体外获得的，应该通过体内动物模型来证实。需要新的治疗性抗生物膜策略，重点是联合治疗的使用，因为生物膜的形成是一个重要的临床问题，因为它们对抗真菌药物具有耐药性。此外，需要对结合了相关微生物区系的烟曲霉菌生物膜进行体内研究。这样的研究将增加我们对烟曲霉菌生物膜在肺入侵过程中的作用的理解的另一层复杂性。
In vivo, Aspergillus fumigatus grows as a typical biofilm with hyphae covered by an extracellular matrix (ECM) composed of polysaccharides, galactomannan, and galactosaminogalactan. alpha 1,3 glucans and melanin are also constitutive of the ECM in aspergilloma but not in invasive aspergillosis. In vitro, two biofilm models were established to mimic the in vivo situation. The first model (model 1) uses submerged liquid conditions and is characterized by slow growth, while the second model (model 2) uses agar medium and aerial conditions and is characterized by rapid growth. The composition of the ECM was studied only in the second model and has been shown to be composed of galactomannan, galactosaminogalactan (GAG), and a1,3 glucans, melanin, antigens, and hydrophobins. The presence of extracellular DNA was detected in model 1 biofilm but not in model 2. Transcriptomic analysis employing both biofilm models showed upregulation of genes coding for proteins involved in the biosynthesis of secondary metabolites, adhesion, and drug resistance. However, most data on A. fumigatus biofilms have been obtained in vitro and should be confirmed using in vivo animal models. There is a need for new therapeutic antibiofilm strategies that focus on the use of combination therapy, since biofilm formation poses an important clinical problem due to their resistance to antifungal agents. Furthermore, in vivo investigations of A. fumigatus biofilms that incorporate the associated microbiota are needed. Such studies will add another layer of complexity to our understanding of the role of A. fumigatus biofilm during lung invasion.