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首页> 外文期刊>Applied Microbiology >Amino Sugars Enhance the Competitiveness of Beneficial Commensals with Streptococcus mutans through Multiple Mechanisms
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Amino Sugars Enhance the Competitiveness of Beneficial Commensals with Streptococcus mutans through Multiple Mechanisms

机译:氨基糖通过多种机制增强变形链球菌的有益功效。

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Biochemical and genetic aspects of the metabolism of the amino sugars N -acetylglucosamine (GlcNAc) and glucosamine (GlcN) by commensal oral streptococci and the effects of these sugars on interspecies competition with the dental caries pathogen Streptococcus mutans were explored. Multiple S. mutans wild-type isolates displayed long lag phases when transferred from glucose-containing medium to medium with GlcNAc as the primary carbohydrate source, but commensal streptococci did not. Competition in liquid coculture or dual-species biofilms between S. mutans and Streptococcus gordonii showed that S. gordonii was particularly dominant when the primary carbohydrate was GlcN or GlcNAc. Transcriptional and enzymatic assays showed that the catabolic pathway for GlcNAc was less highly induced in S. mutans than in S. gordonii . Exposure to H_(2)O_(2), which is produced by S. gordonii and antagonizes the growth of S. mutans , led to reduced mRNA levels of nagA and nagB in S. mutans . When the gene for the transcriptional regulatory NagR was deleted in S. gordonii , the strain produced constitutively high levels of nagA (GlcNAc-6-P deacetylase), nagB (GlcN-6-P deaminase), and glmS (GlcN-6-P synthase) mRNA. Similar to NagR of S. mutans (NagR_(Sm)), the S. gordonii NagR protein (NagR_(Sg)) could bind to consensus binding sites ( dre ) in the nagA , nagB , and glmS promoter regions of S. gordonii . Notably, NagR_(Sg) binding was inhibited by GlcN-6-P, but G-6-P had no effect, unlike for NagR_(Sm). This study expands the understanding of amino sugar metabolism and NagR-dependent gene regulation in streptococci and highlights the potential for therapeutic applications of amino sugars to prevent dental caries.IMPORTANCE Amino sugars are abundant in the biosphere, so the relative efficiency of particular bacteria in a given microbiota to metabolize these sources of carbon and nitrogen might have a profound impact on the ecology of the community. Our investigation reveals that several oral commensal bacteria have a much greater capacity to utilize amino sugars than the dental pathogen Streptococcus mutans and that the ability of the model commensal Streptococcus gordonii to compete against S. mutans is substantively enhanced by the presence of amino sugars commonly found in the oral cavity. The mechanisms underlying the greater capacity and competitive enhancements of the commensal are shown to depend on how the genes for the catabolic enzymes are regulated, the role of the allosteric modulators affecting such regulation, and the ability of amino sugars to enhance certain activities of the commensal that are antagonistic to S. mutans .
机译:常见的口服链球菌对氨基糖N-乙酰氨基葡萄糖(GlcNAc)和氨基葡萄糖(GlcN)的代谢的生化和遗传方面的研究,以及这些糖对与龋齿病原体变形链球菌竞争的种间竞争的影响。当从含葡萄糖的培养基转移到以GlcNAc为主要碳水化合物来源的培养基中时,多种变形链球菌野生型分离株显示出较长的滞后阶段,而共生链球菌则没有。变形链球菌和戈登链球菌在液体共培养或双物种生物膜中的竞争表明,当主要碳水化合物为GlcN或GlcNAc时,戈登链球菌特别占优势。转录和酶法分析表明,GlcNAc的分解代谢途径在变形链球菌中的诱导程度低于戈登氏酵母。暴露于戈登氏链球菌产生的H_(2)O_(2)并拮抗变形链球菌的生长,导致变形链球菌nagA和nagB的mRNA水平降低。当在戈登氏酵母中缺失转录调节性NagR的基因时,该菌株产生了组成型高水平的nagA(GlcNAc-6-P脱乙酰基酶),nagB(GlcN-6-P脱氨酶)和glmS(GlcN-6-P)。合酶)mRNA。类似于变形链球菌的NagR(NagR_(Sm)),戈登氏链球菌NagR蛋白(NagR_(Sg))可以与戈氏链球菌nagA,nagB和glmS启动子区域的共有结合位点(dre)结合。值得注意的是,与NagR_(Sm)不同,GlcN-6-P抑制了NagR_(Sg)的结合,但G-6-P没有作用。这项研究拓宽了对链球菌中氨基糖代谢和NagR依赖性基因调控的理解,并突出了氨基糖在预防龋齿方面的治疗应用潜力。重要性氨基糖在生物圈中很丰富,因此特定细菌在细菌中的相对效率如果微生物能够代谢这些碳和氮源,则可能会对社区的生态产生深远影响。我们的研究表明,与口腔病原体变形链球菌相比,几种口腔共生细菌具有更大的利用氨基糖的能力,并且由于普遍存在的氨基糖的存在,模型共生戈登氏链球菌与变形链球菌竞争的能力大大增强。在口腔中。共生糖的更大能力和竞争性增强的潜在机制据显示取决于分解代谢酶基因的调控方式,变构调节剂影响此类调控的作用以及氨基糖增强共生糖的某些活性的能力。与变形链球菌拮抗。

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