Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria
研究膜改变作为致龋细菌耐酸机制
基本信息
- 批准号:10915839
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Dental caries is the most common chronic infectious disease globally and is caused by the formation of acid-producing bacterial biofilms on the tooth surface, which demineralize and destroy the protective underlying enamel barrier. Although the efficacy of fluoride treatments (the contemporary standard in caries prevention) is well-documented, the current prevalence of the disease clearly illustrates that fluoride alone is insufficient to prevent caries in many situations. Therefore, increased understanding of disease pathogenesis and exploration of novel preventative strategies are objectives worthy of attention. Regardless of the microbial taxa involved, bacterial acid-tolerance is an indispensable factor in caries pathogenesis. The known caries pathogen Streptococcus mutans increases the proportion of unsaturated fatty acids (UFAs) in its plasma membrane in response to environmental acidification—an adaptation required for acid-tolerance and virulence. Preliminary data indicates that several other Gram-positive oral taxa, including the caries-associated species, Lactobacillus casei, modify their membranes in a similar manner in response to environmental acidification. This proposal addresses a number of currently unanswered questions raised by these observations. Aims 1 and 2 of the proposed research will determine the scope of this response to acid stress across the oral microbiome, in single
taxa or in a community setting. Aim 3 of this proposal will elucidate how these UFAs are protective against acid-mediated damage. These aims will be accomplished using bioinformatics tools, basic molecular microbiology, an ecologically-relevant and complex in vitro oral biofilm model, and mass spectrometry/lipidomics. Successful completion of the proposed research will answer pertinent questions regarding caries pathogenesis in a multispecies setting and is likely to open the door to investigation of novel anti-caries therapeutics which, while targeting acidophiles, function regardless of the presence and abundance of S. mutans. The candidate, Dr. Jonathon Baker, has a longstanding interest in the microbiology of dental caries. Upon completion of the K99 (mentored) phase of this award, his goal is to become an independent PI at a leading research university, where he plans to continue research on the modifications that bacteria make to their membranes to combat environmental stresses, while leveraging acquired data to develop novel therapeutics. A funded K99/R00 proposal will allow Dr. Baker to develop skills necessary to both complete the proposed research (training in mass spectrometry/lipidomics) and subsequently become an independent research scientist (training in didactic lecturing, mentoring, and grantsmanship). Dr. Baker’s mentors and environment: Drs. Karen Nelson (J. Craig Venter Institute), Anna Edlund (J. Craig Venter Institute/UC San Diego), Pieter Dorrestein (UC San Diego), Victor Nizet (UC San Diego) and Robert Quivey, Jr. (University of Rochester School of Medicine and Dentistry) have been carefully selected to provide high-quality, diverse scientific and collegial support, as well as state-of-the-art facilities, to ensure successful completion of this research program and the proposed career development goals.
龋齿是全球最常见的慢性传染病,是由牙齿表面形成产酸细菌生物膜引起的,这种细菌生物膜会脱矿并破坏底层的牙釉质屏障,尽管氟化物治疗(龋齿预防的当代标准)的效果不佳。 )有据可查,目前该疾病的流行清楚地表明,在许多情况下单独使用氟化物不足以预防龋齿,因此,无论情况如何,增加对疾病发病机制的了解和探索新的预防策略都是值得关注的目标。涉及微生物类群,细菌耐酸性是龋齿发病机制中不可或缺的因素,已知的龋齿病原体变形链球菌会增加其质膜中不饱和脂肪酸(UFA)的比例,以响应环境酸化——这是耐酸和耐酸所需的适应。初步数据表明,其他几种革兰氏阳性口腔类群,包括与龋齿相关的物种干酪乳杆菌,以类似的方式改变其膜。该提案解决了这些观察结果提出的一些目前尚未解答的问题,该研究的目标 1 和 2 将确定整个口腔微生物组对酸应激的反应范围。
该提案的目标 3 将阐明这些 UFA 如何防止酸介导的损伤。这些目标将使用生物信息学工具、基本分子微生物学、生态相关且复杂的体外口腔生物膜模型。质谱/脂质组学的成功完成将回答有关多物种环境中龋齿发病机制的相关问题,并可能为新的研究打开大门。抗龋齿疗法在针对嗜酸菌的同时,无论是否存在变形链球菌,也能发挥作用。 候选人乔纳森·贝克 (Jonathon Baker) 博士在完成 K99(指导)阶段后,对龋齿微生物学有着长期的兴趣。获得该奖项后,他的目标是成为一所领先研究型大学的独立 PI,他计划在那里继续研究细菌对其细胞膜进行的修饰以对抗环境压力,同时利用获得的数据开发 A 资助的新型疗法。 K99/R00 提案将使贝克博士能够发展必要的技能,以完成拟议的研究(质谱/脂质组学培训),并随后成为一名独立研究科学家(教学讲座、指导和贝克博士导师的培训)。和环境:Karen Nelson 博士(J. Craig Venter 研究所)、Anna Edlund(J. Craig Venter 研究所/加州大学圣地亚哥分校)、Pieter Dorrestein(加州大学圣地亚哥分校)、Victor Nizet(加州大学圣地亚哥分校)和 Robert Quivey, Jr.(罗切斯特大学医学和牙科学院)经过精心挑选,可提供高质量、多样化的科学和学院支持以及最先进的设施,确保成功完成本研究计划和拟议的职业发展目标。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jonathon Baker其他文献
Jonathon Baker的其他文献
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{{ truncateString('Jonathon Baker', 18)}}的其他基金
Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria
研究膜改变作为致龋细菌耐酸机制
- 批准号:
10624648 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria
研究膜改变作为致龋细菌耐酸机制
- 批准号:
10054501 - 财政年份:2020
- 资助金额:
$ 24.9万 - 项目类别:
Investigating Membrane Alterations as a Mechanism of Acid Tolerance in Cariogenic Bacteria
研究膜改变作为致龋细菌耐酸机制
- 批准号:
10174917 - 财政年份:2020
- 资助金额:
$ 24.9万 - 项目类别:
Understanding S. Mutans Pathogenesis in a Social and Ecological Setting
了解社会和生态环境中变形链球菌的发病机制
- 批准号:
9617563 - 财政年份:2018
- 资助金额:
$ 24.9万 - 项目类别:
Understanding S. mutans pathogenesis in a social and ecological setting
了解社会和生态环境中变形链球菌的发病机制
- 批准号:
9327360 - 财政年份:2017
- 资助金额:
$ 24.9万 - 项目类别:
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