Purpose

The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains.

Methods

We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets.

Results

We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response.

Conclusion

Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus.

中文翻译：

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万古霉素敏感和万古霉素中度耐药金黄色葡萄球菌的蛋白质组学比较分析

目的

万古霉素的广泛使用导致金黄色葡萄球菌菌株的发展，对万古霉素具有不同程度的耐药性。本研究旨在通过对万古霉素中度耐药金黄色葡萄球菌（VISA）和万古霉素敏感金黄色葡萄球菌（VSSA）菌株中分离的亚细胞组分进行蛋白质组学分析，探讨万古霉素耐药的分子原因。

方法

我们对从 2 个同基因金黄色葡萄球菌菌株中分离的亚细胞组分进行了蛋白质组学分析：菌株 11 (VSSA) 和菌株 11Y (VISA)。我们采用生物信息学分析辅助的综合定量蛋白质组学方法，全面研究了蛋白质组谱。使用密集的生物信息学分析，包括蛋白质注释、功能分类、功能富集和基于功能富集的聚类分析，来注释可量化的目标。

结果

与菌株11相比，我们在菌株11Y中鉴定出128个上调蛋白和21个下调蛋白。最大的差异表达蛋白组由与代谢和催化活性相关的酶蛋白组成，分别占总蛋白的32.1%和50%，分别。一些蛋白质是金黄色葡萄球菌调节网络中不可或缺的部分，万古霉素处理会改变这些蛋白质，这些蛋白质与细胞壁代谢、细胞粘附、蛋白水解和压力反应有关。

结论

我们的蛋白质组学研究揭示了与金黄色葡萄球菌万古霉素耐药性相关的调节蛋白。其中一些蛋白质参与细胞代谢和功能的调节，这为开发管理金黄色葡萄球菌万古霉素耐药性的策略提供了潜在的靶标。