Phosphate homeostasis and uptake in Staphylococcus aureus

金黄色葡萄球菌的磷酸盐稳态和摄取

基本信息

项目摘要

Project Summary / Abstract Phosphate is an essential nutrient that contributes to all aspects of cellular physiology. Despite its essentiality, phosphate can also be toxic, thus regulation of phosphate uptake and homeostasis is critical for all forms of life. This is exemplified by the observation that disrupting these processes reduces the virulence of many enterobacterial pathogens. Staphylococcus aureus is a devastating pathogen that is a serious threat to human health due to the continued emergence of antibiotic resistance. Surprisingly, neither phosphate uptake nor homeostasis have been systematically studied in S. aureus. This is despite the fact that phosphate homeostasis in S. aureus is linked to changes in daptomycin resistance. Phosphate homeostasis has been most comprehensively studied in Escherichia coli where it is controlled by a two-component system known as PhoBR (PhoPR in S. aureus). In E. coli, the activity of PhoBR is controlled by the PstSCAB phosphate transporter and the PhoU accessory protein. Loss of either PstSCAB or PhoU in E. coli and other bacteria results in constitutive activation of PhoBR. Preliminary investigations have revealed that S. aureus possesses three phosphate transporters, PstSCAB, PitA, and NptA, that expand the environments where S. aureus can obtain phosphate and contribute to infection. In S. aureus, both PstSCAB and NptA, but not PitA, are dependent on PhoPR for expression. Further differing from E. coli, S. aureus possesses three PhoU homologs, one associated with each transporter. Surprisingly, loss of either PstSCAB or the canonical PhoU homolog does not result in constitutive activation of PhoPR in S. aureus. These and other observations demonstrate that phosphate homeostasis in S. aureus differs from established models. Loss of PhoPR or PstSCAB and NptA reduces the ability of S. aureus to cause infection. Intriguingly, the phoPR and pstSCABnptA mutants do not phenocopy each other. The phoPR mutant has a reduced ability to grow in phosphate-limited environments and cause infection relative to the transporter double mutant. These observations indicate that PhoPR regulates additional unknown transporter-independent factors that enable S. aureus to survive phosphate limitation and cause disease. Together, these observations lead to the hypothesis that an expanded repertoire of regulatory proteins controls phosphate homeostasis in S. aureus and that disruption of this regulatory network reduces staphylococcal virulence. The two Aims of this proposal will test this hypothesis and elucidate the factors controlled by PhoPR that enable S. aureus to cause infection. Aim I will determine the contribution of PhoPR to S. aureus phosphate homeostasis and virulence. Aim II will evaluate the contribution of the three PhoU homologs possessed by S. aureus to controlling phosphate homeostasis.
项目概要/摘要 磷酸盐是一种必需营养素,有助于细胞生理学的各个方面。尽管其重要性, 磷酸盐也可能有毒,因此调节磷酸盐的吸收和体内平衡对于所有生命形式都至关重要。 观察到破坏这些过程可以降低许多病毒的毒力就证明了这一点。 肠细菌病原体。金黄色葡萄球菌是一种破坏性病原体,对人类造成严重威胁 由于抗生素耐药性不断出现,健康状况受到影响。令人惊讶的是,磷酸盐吸收和 金黄色葡萄球菌的体内平衡已得到系统研究。尽管事实上磷酸盐稳态 金黄色葡萄球菌中的细菌与达托霉素耐药性的变化有关。磷酸盐稳态最 在大肠杆菌中进行了全面研究,该大肠杆菌由称为 PhoBR 的双组分系统控制 (金黄色葡萄球菌中的 PhoPR)。在大肠杆菌中,PhoBR 的活性由 PstSCAB 磷酸盐转运蛋白控制,并且 PhoU 辅助蛋白。大肠杆菌和其他细菌中 PstSCAB 或 PhoU 的丢失会导致组成型 PhoBR 的激活。初步调查显示,金黄色葡萄球菌具有三种磷酸盐 转运蛋白 PstSCAB、PitA 和 NptA,扩大金黄色葡萄球菌获取磷酸盐的环境 并助长感染。在金黄色葡萄球菌中,PstSCAB 和 NptA(但不包括 PitA)都依赖于 PhoPR 表达。与大肠杆菌进一步不同的是,金黄色葡萄球菌拥有三种 PhoU 同源物,每一种都与 运输者。令人惊讶的是,PstSCAB 或典型 PhoU 同系物的丢失不会导致组成型 金黄色葡萄球菌中 PhoPR 的激活。这些和其他观察结果表明,S. 中的磷酸盐稳态。 金黄色葡萄球菌与已建立的模型不同。 PhoPR 或 PstSCAB 和 NptA 的缺失会降低金黄色葡萄球菌的能力 以引起感染。有趣的是,phoPR 和pstSCABnptA 突变体并不相互表型复制。这 相对于磷酸盐限制的环境,phoPR 突变体的生长能力和引起感染的能力降低 转运蛋白双突变体。这些观察结果表明 PhoPR 调节额外的未知 使金黄色葡萄球菌能够在磷酸盐限制下生存并引起疾病的独立于转运蛋白的因素。 总之,这些观察结果得出这样的假设:调节蛋白的扩展库控制 金黄色葡萄球菌中的磷酸盐稳态,并且该调节网络的破坏会减少葡萄球菌 毒力。该提案的两个目标将检验这一假设并阐明 PhoPR 控制的因素 使金黄色葡萄球菌能够引起感染。目标 I 将确定 PhoPR 对金黄色葡萄球菌磷酸盐的贡献 稳态和毒力。 Aim II 将评估 S. 拥有的三个 PhoU 同系物的贡献。 金黄色葡萄球菌控制磷酸盐稳态。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Thomas Everett Kehl-Fie其他文献

Thomas Everett Kehl-Fie的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Thomas Everett Kehl-Fie', 18)}}的其他基金

Leveraging host-imposed metal starvation to elucidate the molecular and environmental factors that dictate metal utilization by the iron/manganese superoxide dismutase superfamily
利用宿主施加的金属饥饿来阐明决定铁/锰超氧化物歧化酶超家族利用金属的分子和环境因素
  • 批准号:
    10294718
  • 财政年份:
    2021
  • 资助金额:
    $ 18.42万
  • 项目类别:
Leveraging host-imposed metal starvation to elucidate the molecular and environmental factors that dictate metal utilization by the iron/manganese superoxide dismutase superfamily
利用宿主施加的金属饥饿来阐明决定铁/锰超氧化物歧化酶超家族利用金属的分子和环境因素
  • 批准号:
    10407651
  • 财政年份:
    2021
  • 资助金额:
    $ 18.42万
  • 项目类别:
Leveraging host-imposed metal starvation to elucidate the molecular and environmental factors that dictate metal utilization by the iron/manganese superoxide dismutase superfamily
利用宿主施加的金属饥饿来阐明决定铁/锰超氧化物歧化酶超家族利用金属的分子和环境因素
  • 批准号:
    10617269
  • 财政年份:
    2021
  • 资助金额:
    $ 18.42万
  • 项目类别:
Overcoming nutritional immunity: Staphylococcal adaptation to host-imposed manganese and zinc starvation
克服营养免疫:葡萄球菌对宿主造成的锰和锌饥饿的适应
  • 批准号:
    9176192
  • 财政年份:
    2016
  • 资助金额:
    $ 18.42万
  • 项目类别:
Overcoming nutritional immunity: Staphylococcal adaptation to host-imposed manganese and zinc starvation
克服营养免疫:葡萄球菌对宿主造成的锰和锌饥饿的适应
  • 批准号:
    9927982
  • 财政年份:
    2016
  • 资助金额:
    $ 18.42万
  • 项目类别:
Adaptation of Staphylococcus aureus to Mn and Zn starvation imposed by the host
金黄色葡萄球菌对宿主造成的锰和锌饥饿的适应
  • 批准号:
    8814169
  • 财政年份:
    2014
  • 资助金额:
    $ 18.42万
  • 项目类别:
Adaptation of Staphylococcus aureus to Mn and Zn starvation imposed by the host
金黄色葡萄球菌对宿主造成的锰和锌饥饿的适应
  • 批准号:
    8487526
  • 财政年份:
    2014
  • 资助金额:
    $ 18.42万
  • 项目类别:
Adaptation of Staphylococcus aureus to Mn-limitation imposed by the host
金黄色葡萄球菌对宿主施加的锰限制的适应
  • 批准号:
    8620543
  • 财政年份:
    2012
  • 资助金额:
    $ 18.42万
  • 项目类别:
Adaptation of Staphylococcus aureus to Mn-limitation imposed by the host
金黄色葡萄球菌对宿主施加的锰限制的适应
  • 批准号:
    8316652
  • 财政年份:
    2012
  • 资助金额:
    $ 18.42万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 18.42万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了