Analysis of the Streptococcus mutans Proteome during Acid and Oxidative Stress Reveals Modules of Protein Coexpression and an Expanded Role for the TreR Transcriptional Regulator.
Analysis of the Streptococcus mutans Proteome during Acid and Oxidative Stress Reveals Modules of Protein Coexpression and an Expanded Role for the TreR Transcriptional Regulator.
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DOI：
10.1128/msystems.01272-21
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发表时间：
2022-04-26
期刊：
影响因子：
6.4
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中科院分区：
文献类型：
--
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变形链球菌在口腔微生物群中促进牙齿损伤的生态失调，因为它可以形成生物膜，并且比其大多数生态竞争对手更好地在酸压力下生存，这些竞争对手通常与健康相关。许多这类化合物产生过氧化氢，因此，S。变异体必须通过协调和复杂的生理反应来管理氧化应激和酸应激。本研究对S.在酸和氧化应激以及氧化应激表型受损的缺失突变体Δnox和ΔtreR中，在调节生长期间检查了变形杆菌。总共有607种蛋白质在测试条件下表现出显着不同的丰度，相关网络分析确定了共表达蛋白质的模块，这些蛋白质响应于NOx和/或TreR的缺失以及酸和氧化应激。这些数据解释了ΔtreR菌株表现出的活性氧（ROS）敏感和突变素缺陷表型。SMU.1069-1070是一种知之甚少的LytTR系统，在ΔtreR菌株中的丰度升高。S. LytTR系统调节突变蛋白的产生和能力，这可以解释TreR如何影响突变蛋白的产生。此外，产生变形杆菌素（一种在ROS耐受性中重要的脂肽）的蛋白质簇在ΔtreR菌株中显示出减少的丰度。还强调了Nox在氧化应激反应中的关键作用。至关重要的是，该数据集为口腔健康研究人员提供了一个蛋白质组图谱，这将使他们能够更完整地了解S。变形菌的应激反应是发病所需的，并将促进新的和改进的治疗方法的发展龋齿。重要性龋齿是世界范围内最常见的慢性传染病，对边缘化社会经济群体的影响尤为严重。变形链球菌被认为是龋病的主要病原体，其致病性依赖于协调的生理应激反应，这些应激反应减轻牙菌斑内常见的氧化和酸应激引起的损伤。本研究对S.在酸性和氧化应激以及nox和treR缺失突变体中生长期间检查了变形杆菌。在菌株/生长条件下，总共有607种蛋白质差异表达，并鉴定了共表达蛋白质的模块，这使得能够绘制S.变形菌代谢TreR的存在与通过LytTR系统信号传导的突变蛋白产生和通过变抗菌素产生的氧化应激有关。本研究提供的数据将指导未来的研究阐明S。变形菌的发病机制和开发改进的龋齿预防和治疗模式。
Streptococcus mutans promotes a tooth-damaging dysbiosis in the oral microbiota because it can form biofilms and survive acid stress better than most of its ecological competitors, which are typically health associated. Many of these commensals produce hydrogen peroxide; therefore, S. mutans must manage both oxidative stress and acid stress with coordinated and complex physiological responses. In this study, the proteome of S. mutans was examined during regulated growth in acid and oxidative stresses as well as in deletion mutants with impaired oxidative stress phenotypes, Δnox and ΔtreR. A total of 607 proteins exhibited significantly different abundances across the conditions tested, and correlation network analysis identified modules of coexpressed proteins that were responsive to the deletion of nox and/or treR as well as acid and oxidative stress. The data explained the reactive oxygen species (ROS)-sensitive and mutacin-deficient phenotypes exhibited by the ΔtreR strain. SMU.1069-1070, a poorly understood LytTR system, had an elevated abundance in the ΔtreR strain. S. mutans LytTR systems regulate mutacin production and competence, which may explain how TreR affects mutacin production. Furthermore, the protein cluster that produces mutanobactin, a lipopeptide important in ROS tolerance, displayed a reduced abundance in the ΔtreR strain. The role of Nox as a keystone in the oxidative stress response was also emphasized. Crucially, this data set provides oral health researchers with a proteome atlas that will enable a more complete understanding of the S. mutans stress responses that are required for pathogenesis, and will facilitate the development of new and improved therapeutic approaches for dental caries. IMPORTANCE Dental caries is the most common chronic infectious disease worldwide and disproportionately affects marginalized socioeconomic groups. Streptococcus mutans is considered a primary etiological agent of caries, with its pathogenicity being dependent on coordinated physiological stress responses that mitigate the damage caused by the oxidative and acid stress common within dental plaque. In this study, the proteome of S. mutans was examined during growth in acidic and oxidative stresses as well in nox and treR deletion mutants. A total of 607 proteins were differentially expressed across the strains/growth conditions, and modules of coexpressed proteins were identified, which enabled mapping the acid and oxidative stress responses across S. mutans metabolism. The presence of TreR was linked to mutacin production via LytTR system signaling and to oxidative stress via mutanobactin production. The data provided by this study will guide future research elucidating S. mutans pathogenesis and developing improved preventative and treatment modalities for dental caries.
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