LIBRO - Biofilm Research Laboratory Rosário Oliveira, CEB - Center of Biological Engineering, University of Minho, Gualtar Campus, 4715-057 Braga, Portugal.
i3S - Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal.
Biochem J. 2021 Feb 26;478(4):961-974. doi: 10.1042/BCJ20200844.
Candida glabrata is a clinically relevant human pathogen with the ability to form high recalcitrant biofilms that contribute to the establishment and persistence of infection. A defining trait of biofilms is the auto-produced matrix, which is suggested to have structural, virulent and protective roles. Thus, elucidation of matrix components, their function and modulation by the host environment is crucial to disclose their role in C. glabrata pathogenesis. As a major step toward this end, this study aimed to reveal, for the first time, the matrix proteome of C. glabrata biofilms, to characterize it with bioinformatic tools and to study its modulation by the environmental pH (acidic and neutral). The results showed the presence of several pH-specific matrix proteins (51 acidic- and 206 neutral-specific) and also proteins commonly found at both pH conditions (236). Of note, several proteins related to mannan and β-glucan metabolism, which have a potential role in the delivery/organization of carbohydrates in the matrix, were found in both pH conditions but in much higher quantity under the neutral environment. Additionally, several virulence-related proteins, including epithelial adhesins, yapsins and moonlighting enzymes, were found among matrix proteins. Importantly, several proteins seem to have a non-canonical secretion pathway and Pdr1 was found to be a potential regulator of matrix proteome. Overall, this study indicates a relevant impact of environmental cues in the matrix proteome and provides a unique resource for further functional investigation of matrix proteins, contributing to the identification of potential targets for the development of new therapies against C. glabrata biofilms.
光滑念珠菌是一种具有形成高抗性生物膜能力的临床相关人类病原体，生物膜有助于感染的建立和持续。生物膜的一个定义特征是自动产生的基质，它被认为具有结构、毒力和保护作用。因此，阐明基质成分、它们的功能以及宿主环境的调节对揭示它们在光滑念珠菌发病机制中的作用至关重要。为此，本研究旨在首次揭示光滑念珠菌生物膜的基质蛋白质组，并用生物信息学工具对其进行表征，并研究其在环境 pH（酸性和中性）下的调节。结果表明，存在几种 pH 特异性基质蛋白（51 种酸性和 206 种中性特异性），以及在两种 pH 条件下都常见的蛋白（236 种）。值得注意的是，几种与甘露聚糖和β-葡聚糖代谢有关的蛋白，它们在基质中碳水化合物的输送/组织中具有潜在作用，在两种 pH 条件下都有发现，但在中性环境下的数量要多得多。此外，还发现了几种与毒力相关的蛋白，包括上皮黏附素、yapsins 和月光酶。重要的是，几种蛋白似乎具有非典型的分泌途径，并且 Pdr1 被发现是基质蛋白质组的潜在调节剂。总的来说，本研究表明环境线索对基质蛋白质组有重要影响，并为进一步研究基质蛋白的功能提供了独特的资源，有助于确定针对光滑念珠菌生物膜的新治疗方法的潜在靶标。
