Abstract:
The major oral odor compound methyl mercaptan (CH3SH) is strongly associated with halitosis and periodontitis. CH3SH production stems from the metabolism of polymicrobial communities in periodontal pockets and on the tongue dorsum. However, understanding of CH3SH-producing oral bacteria and their interactions is limited. This study aimed to investigate CH3SH production by major oral bacteria and the impact of interspecies interactions on its generation. Using a newly constructed large-volume anaerobic noncontact coculture system, Fusobacterium nucleatum was found to be a potent producer of CH3SH, with that production stimulated by metabolic interactions with Streptococcus gordonii, an early dental plaque colonizer. Furthermore, analysis of extracellular amino acids using an S. gordonii arginine-ornithine antiporter (ArcD) mutant demonstrated that ornithine excreted from S. gordonii is a key contributor to increased CH3SH production by F. nucleatum. Further study with 13C, 15N-methionine, as well as gene expression analysis, revealed that ornithine secreted by S. gordonii increased the demand for methionine through accelerated polyamine synthesis by F. nucleatum, leading to elevated methionine pathway activity and CH3SH production. Collectively, these findings suggest that interaction between S. gordonii and F. nucleatum plays a key role in CH3SH production, providing a new insight into the mechanism of CH3SH generation in oral microbial communities. A better understanding of the underlying interactions among oral bacteria involved in CH3SH generation can lead to the development of more appropriate prophylactic approaches to treat halitosis and periodontitis. An intervention approach like selectively disrupting this interspecies network could also offer a powerful therapeutic strategy.IMPORTANCEHalitosis can have a significant impact on the social life of affected individuals. Among oral odor compounds, CH3SH has a low olfactory threshold and halitosis is a result of its production. Recently, there has been a growing interest in the collective properties of oral polymicrobial communities, regarded as important for the development of oral diseases, which are shaped by physical and metabolic interactions among community participants. However, it has yet to be investigated whether interspecies interactions have an impact on the production of volatile compounds, leading to the development of halitosis. The present findings provide mechanistic insights indicating that ornithine, a metabolite excreted by Streptococcus gordonii, promotes polyamine synthesis by Fusobacterium nucleatum, resulting in a compensatory increase in demand for methionine, which results in elevated methionine pathway activity and CH3SH production. Elucidation of the mechanisms related to CH3SH production is expected to lead to the development of new strategies for managing halitosis.
摘要:
主要的口腔气味化合物甲硫醇(CH3SH)与口臭和牙周炎密切相关。CH3SH的产生源于牙周袋和舌背的多微生物群落的代谢。然而,对产生CH3SH的口腔细菌及其相互作用的了解有限。本研究旨在研究主要口腔细菌的CH3SH生产以及种间相互作用对其产生的影响。使用新建的大容量厌氧非接触共培养系统,核梭杆菌被发现是CH3SH的有效生产者,与戈顿链球菌的代谢相互作用刺激了这种生产,早期牙菌斑定植剂.此外,使用S.gordonii精氨酸-鸟氨酸反转运蛋白(ArcD)突变体分析胞外氨基酸,表明从S.gordonii排泄的鸟氨酸是F.oculatum产生CH3SH增加的关键因素。用13C进一步研究,15N-蛋氨酸,以及基因表达分析,揭示了S.gordonii分泌的鸟氨酸通过加速核仁F.的多胺合成增加了对蛋氨酸的需求,导致蛋氨酸途径活性和CH3SH产量升高。总的来说,这些发现表明,格氏链球菌和核仁F.之间的相互作用在CH3SH生产中起关键作用,为口腔微生物群落中CH3SH的产生机制提供了新的见解。更好地了解参与CH3SH生成的口腔细菌之间的潜在相互作用可以导致开发更合适的预防方法来治疗口臭和牙周炎。像选择性地破坏这种种间网络这样的干预方法也可以提供强大的治疗策略。IMPORTANCEHOTHOTIONS可对受影响个体的社会生活产生重大影响。在口腔气味化合物中,CH3SH的嗅觉阈值较低,口臭是其产生的结果。最近,人们对口腔微生物群落的集体特性越来越感兴趣,被认为对口腔疾病的发展很重要,这是由社区参与者之间的身体和代谢相互作用形成的。然而,物种间的相互作用是否对挥发性化合物的产生有影响还有待研究,导致口臭的发展。目前的发现提供了机械见解,表明鸟氨酸,一种由戈顿链球菌排泄的代谢产物,促进有核梭杆菌合成多胺,导致蛋氨酸需求的补偿性增加,这导致蛋氨酸途径活性升高和CH3SH产生。与CH3SH生产相关的机制的阐明有望导致控制口臭的新策略的开发。