Transcriptome and Proteome of Methicillin-Resistant Staphylococcus aureus Small-Colony Variants Reveal Changed Metabolism and Increased Immune Evasion.
Transcriptome and Proteome of Methicillin-Resistant Staphylococcus aureus Small-Colony Variants Reveal Changed Metabolism and Increased Immune Evasion.
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耐甲氧西林金黄色葡萄球菌小菌落变体的转录组和蛋白质组揭示了代谢的变化和免疫逃避的增加。
DOI：
10.1128/spectrum.01898-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
Wang, Hui
中科院分区：
文献类型：
--
作者：
Liu, Si;Chen, Hongbin;Chen, Juan;Wang, Tianyi;Tu, Shangyu;Zhang, Xiaoyang;Wang, Qi;Yin, Yuyao;Zhang, Yawei;Wang, Xiaojuan;Zhao, Chunjiang;Wang, Hui
耐甲氧西林金黄色葡萄球菌（MRSA）感染已成为公共卫生危机。最近，我们分离出MRSA的小菌落变体（SCV），其特征是生长缓慢，毒力下降，抗生素耐药性增加和免疫逃避。在本研究中，我们提供了临床MRSA序列239型（ST 239）正常菌株和SCV的蛋白质组学和转录组学图谱，并试图确定与SCV形成和存活密切相关的关键基因或途径。提取RNA和蛋白质并进行RNA测序和质谱分析，并通过生物信息学分析评估转录组和蛋白质组。通过功能测定验证了结果。总共鉴定了822个差异表达基因（DEG）和773个差异表达蛋白（DEP）;其中，286个DEG和DEP相关并进行京都百科全书基因和基因组分析。一些途径很重要，包括ABC转运蛋白、核糖体生物发生以及糖酵解/糖异生和柠檬酸循环（三羧酸[TCA]循环）等代谢途径。基于这些结果，我们发现ABC转运蛋白和TCA循环途径的下调导致SCV中电子传递链缺陷和ATP产生减少，导致对糖酵解的依赖及其上调。此外，胶囊多糖的上调和表面蛋白的下调阻止了吞噬作用并减少了宿主细胞的粘附，有助于SCV的免疫逃避。这些发现有助于更好地理解SCV形成和存活的机制。重要性金黄色葡萄球菌的小菌落变体（SCV）引起了越来越多的研究关注。由于其生长缓慢，非典型的菌落形态和不寻常的代谢特征，SCV经常在实验室中引起混乱。此外，SCV的临床治疗具有挑战性，因为它们具有抗生素抗性和免疫逃避，导致持续和复发性感染。然而，其形成的机制仍不清楚。在这项研究中，我们分离了耐甲氧西林的S。并提供了正常菌株和SCV的转录组学和蛋白质组学谱。根据我们的分析，糖酵解上调和TCA循环下调影响电子传递链和能量供应，导致代谢减慢。此外，荚膜生物合成增加，而表面蛋白的数量减少，从而促进SCV的免疫逃避。
Methicillin-resistant Staphylococcus aureus (MRSA) infection has become a public health crisis. Recently, we isolated small-colony variants (SCVs) of MRSA, which are characterized by slow growth, decreased virulence, increased antibiotic resistance, and immune evasion. In the present study, we provided proteomic and transcriptomic profiles of clinical MRSA sequence type 239 (ST239) normal strains and SCVs and attempted to identify the key genes or pathways closely related to SCV formation and survival. RNAs and proteins were extracted and subjected to RNA sequencing and mass spectrometry, and the transcriptome and proteome were evaluated via bioinformatic analysis. The results were verified by functional assays. In total, 822 differentially expressed genes (DEGs) and 773 differentially expressed proteins (DEPs) were identified; of these, 286 DEGs and DEPs were correlated and subjected to Kyoto Encyclopedia Genes and Genomes analysis. Some pathways were significant, including ABC transporters, ribosome biogenesis, and metabolic pathways such as glycolysis/gluconeogenesis and the citrate cycle (tricarboxylic acid [TCA] cycle). Based on these results, we found that the downregulation of ABC transporters and the TCA cycle pathway resulted in electron transport chain deficiencies and reduced ATP production in SCVs, leading to a dependence on glycolysis and its upregulation. In addition, the upregulation of capsule polysaccharides and the downregulation of surface proteins prevented phagocytosis and reduced the adhesion of host cells, contributing to immune evasion by SCVs. These findings contribute to a better understanding of the mechanisms of SCV formation and survival. IMPORTANCE Small-colony variants (SCVs) of Staphylococcus aureus have drawn increasing research attention. Owing to their slow growth, atypical colony morphology, and unusual metabolic characteristics, SCVs often cause confusion in the laboratory. Furthermore, clinical treatment of SCVs is challenging owing to their antibiotic resistance and immune evasion, leading to persistent and recurrent infections. However, the mechanisms underlying their formation remain unclear. In this study, we isolated SCVs of methicillin-resistant S. aureus and provided transcriptomic and proteomic profiles of normal strains and SCVs. Based on our analysis, glycolysis upregulation and TCA cycle downregulation affected the electron transport chain and energy supply, leading to slower metabolism. Moreover, capsular biosynthesis was increased, while the number of surface proteins decreased, thus promoting immune evasion by SCVs.
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影响因子：
3.1
作者：
Lattar, Santiago M.;Tuchscherr, Lorena P. N.;Sordelli, Daniel O.
通讯作者：
Sordelli, Daniel O.
影响因子：
3.4
作者：
BARBER, M
通讯作者：
BARBER, M
影响因子：
4.6
作者：
Ebner, Patrick;Reichert, Sebastian;Goetz, Friedrich
通讯作者：
Goetz, Friedrich
影响因子：
4.6
作者：
Ahmadi, Khadijeh;Aslani, Mohammad M.;Mahdavi, Mehdi
通讯作者：
Mahdavi, Mehdi
DOI：
10.1126/science.aan4665
发表时间：
2018-04-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kornberg MD;Bhargava P;Kim PM;Putluri V;Snowman AM;Putluri N;Calabresi PA;Snyder SH
通讯作者：
Snyder SH