Characterization of the Trehalose Utilization Operon in Streptococcus mutans Reveals that the TreR Transcriptional Regulator Is Involved in Stress Response Pathways and Toxin Production
Characterization of the Trehalose Utilization Operon in Streptococcus mutans Reveals that the TreR Transcriptional Regulator Is Involved in Stress Response Pathways and Toxin Production
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DOI：
10.1128/jb.00057-18
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发表时间：
2018-06-01
影响因子：
3.2
通讯作者：
Quivey, R. G., Jr.
中科院分区：
文献类型：
--
作者：
Baker, J. L.;Lindsay, E. L.;Quivey, R. G., Jr.
变形链球菌是最常与龋齿发展相关的生物体，能够利用各种碳水化合物进行能量代谢。一种这样的分子是海藻糖，一种在人类食物中常见的二糖，其最近被认为与增强病原体艰难梭菌的流行菌株的毒力有关。在这项研究中，所有三个基因缺失的突变体在推定的S。对变形菌海藻糖利用操纵子进行了表征，并且当海藻糖是唯一提供的碳水化合物来源时，所述基因显示为野生型生长水平所需。有趣的是，TreR转录调节因子似乎是关键的响应氧化应激和安装保护性应激耐受反应后，在中等酸性pH值的生长。mRNA测序（RNA-seq）的treR缺失突变体表明，在S。在变形杆菌中，TreR作为tre操纵子转录的海藻糖敏感激活剂，而不是如在其他物种中描述的作为阻遏物。此外，treR的缺失导致了参与遗传能力和细菌素产生的许多基因的下调，支持了最近一项将海藻糖和S.变形能力通路。最后，缺失treR削弱了S.变形链球菌以抑制竞争物种戈登链球菌和乳酸乳球菌的生长。综合以上结果，本研究进一步巩固了S。变形菌tre操纵子在海藻糖利用中的作用，并提出了新的功能，包括在应激反应和竞争适应性中的作用。变形杆菌是龋齿的主要病原体，龋齿是全球最常见的慢性疾病。S.变形菌必须能够在其牙菌斑生态位中胜过细菌生物体，以建立持久性和发病机制。为此，S。变形杆菌代谢各种各样的碳水化合物以产生酸并阻碍其酸敏感的邻居。此外，S.变形杆菌通过与遗传能力相关的途径利用群体信号来诱导毒素的产生以杀死其竞争对手。这项研究明确表明，S.变形菌海藻糖利用操纵子是在海藻糖中生长所必需的。此外，本研究表明，S。10.128/JB通过调节参与遗传能力和毒素产生的基因在毒力中具有新的作用。
Streptococcus mutans, the organism most frequently associated with the development of dental caries, is able to utilize a diverse array of carbohydrates for energy metabolism. One such molecule is trehalose, a disaccharide common in human foods, which has been recently implicated in enhancing the virulence of epidemic strains of the pathogen Clostridium difficile. In this study, mutants with deletions of all three genes in the putative S. mutans trehalose utilization operon were characterized, and the genes were shown to be required for wild-type levels of growth when trehalose was the only carbohydrate source provided. Interestingly, the TreR transcriptional regulator appeared to be critical for responding to oxidative stress and for mounting a protective stress tolerance response following growth at moderately acidic pH. mRNA sequencing (RNA-seq) of a treR deletion mutant suggested that in S. mutans, TreR acts as a trehalose-sensing activator of transcription of the tre operon, rather than as a repressor, as described in other species. In addition, deletion of treR caused the downregulation of a number of genes involved in genetic competence and bacteriocin production, supporting the results of a recent study linking trehalose and the S. mutans competence pathways. Finally, deletion of treR compromised the ability of S. mutans to inhibit the growth of the competing species Streptococcus gordonii and Lactococcus lactis. Taking the results together, this study solidifies the role of the S. mutans tre operon in trehalose utilization and suggests novel functions for the TreR regulator, including roles in the stress response and competitive fitness.IMPORTANCE S. mutans is the primary etiologic agent of dental caries, which globally is the most common chronic disease. S. mutans must be able to outcompete commensal organisms in its dental plaque niche in order to establish persistence and pathogenesis. To that end, S. mutans metabolizes a diverse array of carbohydrates to generate acid and impede its acid-sensitive neighbors. Additionally, S. mutans utilizes quorum signaling through genetic competence-associated pathways to induce production of toxins to kill its rivals. This study definitively shows that the S. mutans trehalose utilization operon is required for growth in trehalose. Furthermore, this study suggests that the S. mutans TreR transcriptional regulator has a novel role 10.128/JB in virulence through regulation of genes involved in genetic competence and toxin production.