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Novel Entries in a Fungal Biofilm Matrix Encyclopedia

机译：真菌生物膜基质百科全书中的新词条

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Virulence of Candida is linked with its ability to form biofilms. Once established, biofilm infections are nearly impossible to eradicate. Biofilm cells live immersed in a self-produced matrix, a blend of extracellular biopolymers, many of which are uncharacterized. In this study, we provide a comprehensive analysis of the matrix manufactured by Candida?albicans both in vitro and in a clinical niche animal model. We further explore the function of matrix components, including the impact on drug resistance. We uncovered components from each of the macromolecular classes (55% protein, 25% carbohydrate, 15% lipid, and 5% nucleic acid) in the C.?albicans biofilm matrix. Three individual polysaccharides were identified and were suggested to interact physically. Surprisingly, a previously identified polysaccharide of functional importance, β-1,3-glucan, comprised only a small portion of the total matrix carbohydrate. Newly described, more abundant polysaccharides included α-1,2 branched α-1,6-mannans (87%) associated with unbranched β-1,6-glucans (13%) in an apparent mannan-glucan complex (MGCx). Functional matrix proteomic analysis revealed 458 distinct activities. The matrix lipids consisted of neutral glycerolipids (89.1%), polar glycerolipids (10.4%), and sphingolipids (0.5%). Examination of matrix nucleic acid identified DNA, primarily noncoding sequences. Several of the in vitro matrix components, including proteins and each of the polysaccharides, were also present in the matrix of a clinically relevant in vivo biofilm. Nuclear magnetic resonance (NMR) analysis demonstrated interaction of aggregate matrix with the antifungal fluconazole, consistent with a role in drug impedance and contribution of multiple matrix components. >IMPORTANCE This report is the first to decipher the complex and unique macromolecular composition of the Candida biofilm matrix, demonstrate the clinical relevance of matrix components, and show that multiple matrix components are needed for protection from antifungal drugs. The availability of these biochemical analyses provides a unique resource for further functional investigation of the biofilm matrix, a defining trait of this lifestyle.
机译： Candida 的毒力与其形成生物膜的能力有关。一旦建立，生物膜感染几乎是不可能根除的。生物膜细胞生活在一个自我产生的基质中，该基质是细胞外生物聚合物的混合物，其中许多是未知的。在这项研究中，我们提供了 Candida？albicans 在体外和临床小生境动物模型中制造的基质的全面分析。我们进一步探讨了基质成分的功能，包括对耐药性的影响。我们在白色念珠菌生物膜基质中发现了每个大分子类别的成分（55％的蛋白质，25％的碳水化合物，15％的脂质和5％的核酸）。鉴定出三种单独的多糖，并建议它们进行物理相互作用。令人惊讶地，先前鉴定的具有功能重要性的多糖β-1，3-葡聚糖仅占总基质碳水化合物的一小部分。新近描述的更丰富的多糖包括表观甘露聚糖-葡聚糖复合物（MGCx）中与未分支的β-1,6-葡聚糖（13％）相关的α-1,2支化α-1,6-甘露聚糖（87％）。功能矩阵蛋白质组学分析显示458种不同的活动。基质脂质由中性甘油脂（89.1％），极性甘油脂（10.4％）和鞘脂（0.5％）组成。检查基质核酸鉴定的DNA，主要是非编码序列。临床上相关的体内生物膜的基质中也存在几种体外基质成分，包括蛋白质和每种多糖。核磁共振（NMR）分析表明聚集基质与抗真菌药氟康唑的相互作用，与药物抗药性和多种基质成分的作用一致。 >重要性该报告是第一个破译 Candida 生物膜基质的复杂而独特的大分子组成，证明基质成分的临床意义，并表明需要多种基质成分的报告。保护免受真菌药物侵害。这些生物化学分析的可用性为生物膜基质的进一步功能研究提供了独特的资源，生物膜基质是这种生活方式的决定性特征。

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