Fungal biofilm morphology impacts hypoxia fitness and disease progression
Fungal biofilm morphology impacts hypoxia fitness and disease progression
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DOI：
10.1038/s41564-019-0558-7
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发表时间：
2019-12-01
影响因子：
28.3
通讯作者：
Cramer, Robert A.
中科院分区：
文献类型：
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作者：
Kowalski, Caitlin H.;Kerkaert, Joshua D.;Cramer, Robert A.
微生物群体形成复杂的宏观菌落，具有不同的形态，其功能仍有待充分了解。尽管从环境和临床样本中分离的真菌菌落揭示了丰富的种内形态多样性，但尚不清楚这种多样性如何影响真菌适应性和疾病进展。在这里，我们观察到氧气张力对人类真菌病原体烟曲霉的宏观和生物膜形态的显著影响。低氧型是通过亚端粒基因簇的表达产生的，该基因簇包含改变菌丝表面和干扰菌丝间相互作用以破坏体内生物膜和感染部位形态的基因。因此，在侵袭性曲霉病的小鼠模型中，这种形态导致宿主炎症增加，疾病快速进展和死亡率。综上所述，这些数据表明，丝状真菌生物膜形态影响真菌与宿主的相互作用，在评估分离菌株的毒力和宿主疾病进展时应考虑到这一点。
Microbial populations form intricate macroscopic colonies with diverse morphologies whose functions remain to be fully understood. Despite fungal colonies isolated from environmental and clinical samples revealing abundant intraspecies morphological diversity, it is unclear how this diversity affects fungal fitness and disease progression. Here we observe a notable effect of oxygen tension on the macroscopic and biofilm morphotypes of the human fungal pathogen Aspergillus fumigatus. A hypoxia-typic morphotype is generated through the expression of a subtelomeric gene cluster containing genes that alter the hyphal surface and perturb interhyphal interactions to disrupt in vivo biofilm and infection site morphologies. Consequently, this morphotype leads to increased host inflammation, rapid disease progression and mortality in a murine model of invasive aspergillosis. Taken together, these data suggest that filamentous fungal biofilm morphology affects fungal-host interactions and should be taken into consideration when assessing virulence and host disease progression of an isolated strain.