Molecular mechanisms controlling fructose‐specific memory and catabolite repression in lactose metabolism by Streptococcus mutans,Molecular Microbiology

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Molecular mechanisms controlling fructose‐specific memory and catabolite repression in lactose metabolism by Streptococcus mutans
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-09-03 , DOI: 10.1111/mmi.14597
Lin Zeng ₁ , Robert A Burne ₁

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Lactose is an abundant dietary carbohydrate metabolized by the dental pathogen Streptococcus mutans. Lactose metabolism presents both classic diauxic behaviors and long‐term memory, where the bacteria can pause for >11 h before initiating growth on lactose. Here, we explored mechanisms contributing to unusual aspects of regulation of the lac operon. The fructose‐phosphate metabolites, F‐1‐P and F‐6‐P, could modulate the DNA‐binding activities of the lactose repressor. Recombinant LacR proteins bound upstream of lacA and Gal‐6‐P induced the formation of different LacR‐DNA complexes. Deletion of lacR resulted in strain‐specific growth phenotypes on lactose, but also on a number of mono‐ and di‐saccharides that involve the glucose‐PTS or glucokinase in their catabolism. The phenotypes were consistent with the novel findings that loss of LacR altered glucose‐PTS activity and expression of the gene for glucokinase. CcpA was also shown to affect lactose metabolism in vivo and to bind to the lacA promoter region in vitro. Collectively, our study reveals complex molecular circuits controlling lactose metabolism in S. mutans, where LacR and CcpA integrate cellular and environmental cues to regulate metabolism of a variety of carbohydrates that are critical to persistence and pathogenicity of S. mutans.

中文翻译：

变形链球菌在乳糖代谢中控制果糖特异性记忆和分解代谢物抑制的分子机制

乳糖是一种丰富的膳食碳水化合物，由牙科病原体变形链球菌代谢。乳糖代谢表现出经典的双重行为和长期记忆，其中细菌在开始使用乳糖生长之前可以暂停 > 11 小时。在这里，我们探索了有助于调节lac操纵子异常方面的机制。果糖-磷酸代谢物 F-1-P 和 F-6-P 可以调节乳糖阻遏物的 DNA 结合活性。与lacA和 Gal-6-P上游结合的重组 LacR 蛋白诱导不同 LacR-DNA 复合物的形成。lacR 的缺失导致在乳糖上出现菌株特异性生长表型，但也导致许多单糖和双糖在其分解代谢中涉及葡萄糖-PTS 或葡萄糖激酶。这些表型与 LacR 缺失改变葡萄糖-PTS 活性和葡萄糖激酶基因表达的新发现一致。还显示 CcpA 影响体内乳糖代谢并在体外与lacA启动子区域结合。总的来说，我们的研究揭示了控制变形链球菌中乳糖代谢的复杂分子回路，其中 LacR 和 CcpA 整合了细胞和环境线索，以调节对变形链球菌的持久性和致病性至关重要的各种碳水化合物的代谢。

更新日期：2020-09-03

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