Walker Alejandro R, Pham Danniel N, Noeparvar Payam, Peterson Alexandra M, Lipp Marissa K, Lemos Jose A, Zeng Lin
bioRxiv. 2025 Mar 18:2024.10.26.620100. doi: 10.1101/2024.10.26.620100.
Fructose catabolism by Streptococcus mutans is initiated by three PTS transporters yielding either fructose-1-phoshate (F-1-P) or fructose-6-phosphate (F-6-P). Deletion of one such F-1-P-generating PTS, fruI, has been shown to reduce the cariogenicity of S. mutans in rats fed a high-sucrose diet. Moreover, a recent study linked fructose metabolism in S. mutans to a reactive electrophile species (RES) methylglyoxal. Here, we conducted a comparative transcriptomic analysis of exponentially grown S. mutans shocked with 50 mM fructose, 50 mM glucose, 5 mM methylglyoxal, or 0.5 mM hydrogen peroxide (H2O2). The results revealed a striking overlap between the fructose and methylglyoxal transcriptomes, totaling 176 genes, 61 of which were also shared with the H2O2 transcriptome. This core of 61 genes encompassed many of the same pathways affected by exposure to low pH or zinc intoxication. Consistent with these findings, fructose negatively impacted metal homeostasis of a mutant deficient in zinc expulsion and the growth of a mutant of the major oxidative stress regulator SpxA1. We further demonstrated the induction of the superoxide dismutase (sodA) and the fruRKI operon by different levels of fructose. Finally, fructose metabolism lowered culture pH at a faster pace, allowed better survival under acidic and nutrient-depleted conditions, and enhanced the competitiveness of S. mutans against Streptococcus sanguinis, although a moderated level of F-1-P might further boost some of these benefits. In conclusion, fructose metabolism is integrated into the stress core of S. mutans and regulates critical functions required for survival in both the oral cavity and during systemic infections. Importance. Fructose is a common monosaccharide in the biosphere, yet its overconsumption has been linked to various health problems in humans including insulin resistance, obesity, diabetes, and non-alcoholic liver diseases. These effects are in large part attributed to the unique biochemical characteristics and metabolic responses associated with the degradation of fructose. Yet, an understanding of the effects of fructose on the physiology of bacteria and its implications to the human microbiome is severely lacking. Here we performed a series of analyses on the gene regulation of a dental pathogen Streptococcus mutans by exposing it to fructose and other important stress agents. Further supported by growth, persistence, and competition assays, our findings revealed the ability of fructose to activate a set of cellular functions that may prove critical to the ability of the bacterium to persist and cause diseases both within and without of the oral cavity.
变形链球菌对果糖的分解代谢由三种磷酸转移酶系统启动，可产生1-磷酸果糖（F-1-P）或6-磷酸果糖（F-6-P）。已证实，缺失一种产生F-1-P的磷酸转移酶系统fruI，可降低高蔗糖饮食喂养的大鼠体内变形链球菌的致龋性。此外，最近一项研究将变形链球菌中的果糖代谢与活性亲电物质（RES）甲基乙二醛联系起来。在此，我们对指数生长期的变形链球菌进行了比较转录组分析，分别用50 mM果糖、50 mM葡萄糖、5 mM甲基乙二醛或0.5 mM过氧化氢（H2O2）对其进行冲击处理。结果显示，果糖和甲基乙二醛的转录组之间存在显著重叠，共有176个基因，其中61个基因也与H2O2转录组共有。这61个基因的核心包含许多受低pH值暴露或锌中毒影响的相同途径。与这些发现一致，果糖对锌排出缺陷型突变体的金属稳态以及主要氧化应激调节因子SpxA1突变体的生长产生负面影响。我们进一步证明了不同水平的果糖可诱导超氧化物歧化酶（sodA）和fruRKI操纵子。最后，果糖代谢能更快地降低培养基pH值，使其在酸性和营养缺乏条件下具有更好的生存能力，并增强变形链球菌对血链球菌的竞争力，不过适度水平的F-1-P可能会进一步提升其中一些益处。总之，果糖代谢被整合到变形链球菌的应激核心中，并调节其在口腔和全身感染中生存所需的关键功能。重要性。果糖是生物圈中常见的单糖，但其过量摄入与人类的各种健康问题有关，包括胰岛素抵抗、肥胖、糖尿病和非酒精性肝病。这些影响在很大程度上归因于与果糖降解相关的独特生化特性和代谢反应。然而，目前严重缺乏对果糖对细菌生理学影响及其对人类微生物组影响的了解。在此，我们通过将一种口腔病原体变形链球菌暴露于果糖和其他重要应激因子下，对其基因调控进行了一系列分析。通过生长、存活和竞争试验进一步支持，我们的研究结果揭示了果糖激活一组细胞功能的能力，这可能对该细菌在口腔内外持续存在和致病的能力至关重要。
