Reichhardt Courtney, Joubert Lydia-Marie, Clemons Karl V, Stevens David A, Cegelski Lynette
Department of Microbiology, University of Washington, Seattle, Washington, USA.
Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa.
Med Mycol. 2019 Apr 1;57(Supplement_2):S239-S244. doi: 10.1093/mmy/myy140.
The general ability and tendency of bacteria and fungi to assemble into bacterial communities, termed biofilms, poses unique challenges to the treatment of human infections. Fungal biofilms, in particular, are associated with enhanced virulence in vivo and decreased sensitivity to antifungals. Much attention has been given to the complex cell wall structures in fungal organisms, yet beyond the cell surface, Aspergillus fumigatus and other fungi assemble a self-secreted extracellular matrix that is the hallmark of the biofilm lifestyle, protecting and changing the environment of resident members. Elucidation of the chemical and molecular detail of the extracellular matrix is crucial to understanding how its structure contributes to persistence and antifungal resistance in the host. We present a summary of integrated analyses of A. fumigatus biofilm architecture, including hyphae and the extracellular matrix, by scanning electron microscopy and A. fumigatus matrix composition by new top-down solid-state NMR approaches coupled with biochemical analysis. This combined methodology will be invaluable in formulating quantitative and chemical comparisons of A. fumigatus isolates that differ in virulence and are more or less resistant to antifungals. Ultimately, knowledge of the chemical and molecular requirements for matrix formation and function will drive the identification and development of new strategies to interfere with biofilm formation and virulence.
细菌和真菌聚集形成细菌群落（即生物膜）的一般能力和趋势，给人类感染的治疗带来了独特的挑战。特别是真菌生物膜，与体内毒力增强和对抗真菌药物的敏感性降低有关。人们对真菌生物体中复杂的细胞壁结构给予了很多关注，但在细胞表面之外，烟曲霉和其他真菌会组装一种自我分泌的细胞外基质，这是生物膜生活方式的标志，保护并改变了驻留成员的环境。阐明细胞外基质的化学和分子细节对于理解其结构如何导致在宿主体内的持久性和抗真菌耐药性至关重要。我们通过扫描电子显微镜对烟曲霉生物膜结构（包括菌丝和细胞外基质）进行综合分析，并通过新的自上而下的固态核磁共振方法结合生化分析对烟曲霉基质组成进行了总结。这种综合方法对于对毒力不同且或多或少对抗真菌药物有耐药性的烟曲霉分离株进行定量和化学比较将非常有价值。最终，对基质形成和功能的化学和分子要求的了解将推动干扰生物膜形成和毒力的新策略的识别和开发。
