CATABOLITE REPRESSION CONTROLS VIRULENCE IN STREPTOCOCCUS PYOGENES

分解代谢物抑制控制化脓性链球菌的毒力

基本信息

  • 批准号:
    9174072
  • 负责人:
  • 金额:
    $ 34.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-07-01 至 2018-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Restriction of gene expression to a specific phase of the bacterial growth cycle is known as growth phase regulation. For pathogens, it is generally assumed to reflect spatio-temporal adaptations made in response to a dynamic host milieu. However, establishing this link requires identification of specific regulatory elements, their hierarchical relationships, and whether the regulatory network responds in a similar pattern in vivo. Since regulation of virtually all of its recognized virulence factors involves a growth phase component, this issue has emerged as an important concept for understanding the myriad and diverse diseases caused by the important human pathogen Streptococcus pyogenes. Recent work has implicated carbon catabolite regulation (CCR) as an important component of S. pyogenes growth phase regulation, functioning to couple expression of virulence genes to the presence or absence of specific growth substrates. This suggests that substrate availability is a major cue used to distinguish between specific stages of the infection and/or that variation in nutritional signals between different host tissues may drive transcriptome behavior to promote different disease presentations. However, the specific substrates sensed and how any regulator of CCR functions to the control behavior of the S. pyogenes transcriptome in time- and compartment-specific patterns is not well understood and is the subject of this proposal. A CCR regulator known as Carbon Catabolite Protein A (CcpA) makes an important contribution to the temporal regulation of virulence factor genes in S. pyogenes. A major question is how this this single regulator functions to coordinate diverse patterns of gene expression with respect to time. The CcpA pathway is highly conserved among the low G+C firmicutes and elegant studies have revealed the structural basis of how CcpA activity is modulated by multiple co-factors. However, no comprehensive analysis of modes of global regulation that integrates all these regulatory elements has been conducted in any bacterium. The goal of this proposal is to leverage knowledge of CcpA biochemistry along with possible unique properties of S. pyogenes CcpA (spCcpA), a comprehensive examination of S. pyogenes carbohydrate metabolism during infection of soft tissue and an analysis of the energy-producing pathways used for growth in tissue, in order to probe the relationship between growth substrates, temporal control of virulence factor expression, CCR and pathogenesis
描述(由申请人提供):将基因表达限制在细菌生长周期的特定阶段被称为生长阶段调节。对于病原体来说,通常认为它反映了对动态宿主环境的时空适应。然而,建立这种联系需要确定特定的调控元件,它们的层次关系,以及调控网络是否在体内以类似的模式响应。因为几乎所有已知的毒力因子的调控都涉及生长阶段

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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Michael G. Caparon其他文献

Volatile profiling distinguishes emStreptococcus pyogenes/em from other respiratory streptococcal species
挥发性分析区分化脓性链球菌和其他呼吸道链球菌物种
  • DOI:
    10.1128/msphere.00194-23
  • 发表时间:
    2023-09-28
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    Amalia Z. Berna;Joseph A. Merriman;Leah Mellett;Danealle K. Parchment;Michael G. Caparon;Audrey R. Odom John;Jacqueline M. Achkar
  • 通讯作者:
    Jacqueline M. Achkar
Streptococcus pyogenes protein F promotes invasion of HeLa cells.
化脓性链球菌蛋白 F 促进 HeLa 细胞的侵袭。
  • DOI:
    10.1099/00221287-144-11-3079
  • 发表时间:
    1998
  • 期刊:
  • 影响因子:
    1.5
  • 作者:
    Nobuhiko Okada;lchiro Tatsuno;Emanuel Hanski;Michael G. Caparon;C. Sasakawa
  • 通讯作者:
    C. Sasakawa
Reprogramming aerobic metabolism mitigates Streptococcus pyogenes tissue damage in a mouse necrotizing skin infection model
在小鼠坏死性皮肤感染模型中,重新编程有氧代谢可减轻化脓性链球菌组织损伤。
  • DOI:
    10.1038/s41467-025-57348-x
  • 发表时间:
    2025-03-15
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Wei Xu;Tara R. Bradstreet;Zongsen Zou;Suzanne Hickerson;Yuan Zhou;Hongwu He;Brian T. Edelson;Michael G. Caparon
  • 通讯作者:
    Michael G. Caparon
MP23-19 FIBRINOGEN DEPOSITS ON URINARY CATHETERS IN A TIME-DEPENDENT MATTER AND CO-LOCALIZES WITH <em>E. FAECALIS</em> IN PATIENTS WITH POSITIVE <em>E. FAECALIS</em> URINE CULTURES
  • DOI:
    10.1016/j.juro.2017.02.747
  • 发表时间:
    2017-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Tyler M. Bauman;Aaron M. Potretzke;Ana L. Flores-Mireles;Jennifer N. Walker;Alyssa M. Park;Henry L. Schreiber;Jerome S. Pinkner;Michael G. Caparon;Scott J. Hultgren;Alana Desai
  • 通讯作者:
    Alana Desai

Michael G. Caparon的其他文献

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{{ truncateString('Michael G. Caparon', 18)}}的其他基金

Novel Therapeutic Approach to Invasive Group A Streptococcal Disease
侵袭性 A 组链球菌疾病的新治疗方法
  • 批准号:
    10452033
  • 财政年份:
    2022
  • 资助金额:
    $ 34.2万
  • 项目类别:
Novel Therapeutic Approach to Invasive Group A Streptococcal Disease
侵袭性 A 组链球菌疾病的新治疗方法
  • 批准号:
    10546470
  • 财政年份:
    2022
  • 资助金额:
    $ 34.2万
  • 项目类别:
Characterization of assembly factors for type IV secretion systems
IV 型分泌系统组装因子的表征
  • 批准号:
    10435561
  • 财政年份:
    2021
  • 资助金额:
    $ 34.2万
  • 项目类别:
GmPcides: Componds that disarm antibiotic resistance in multiple gram-positive pathogens
GmPcides:解除多种革兰氏阳性病原体抗生素耐药性的化合物
  • 批准号:
    10577811
  • 财政年份:
    2021
  • 资助金额:
    $ 34.2万
  • 项目类别:
GmPcides: Componds that disarm antibiotic resistance in multiple gram-positive pathogens
GmPcides:解除多种革兰氏阳性病原体抗生素耐药性的化合物
  • 批准号:
    10162829
  • 财政年份:
    2021
  • 资助金额:
    $ 34.2万
  • 项目类别:
GmPcides: Componds that disarm antibiotic resistance in multiple gram-positive pathogens
GmPcides:解除多种革兰氏阳性病原体抗生素耐药性的化合物
  • 批准号:
    10352471
  • 财政年份:
    2021
  • 资助金额:
    $ 34.2万
  • 项目类别:
Structure-function analysis of type IVB secretion systems
IVB型分泌系统的结构-功能分析
  • 批准号:
    10624264
  • 财政年份:
    2019
  • 资助金额:
    $ 34.2万
  • 项目类别:
EBPA-FIBROGEN INTERACTION IN ENTEROCOCCUS FAECALIS CAUTI
粪肠球菌中 EBPA-纤维原的相互作用
  • 批准号:
    9304949
  • 财政年份:
    2014
  • 资助金额:
    $ 34.2万
  • 项目类别:
EBPA-FIBROGEN INTERACTION IN ENTEROCOCCUS FAECALIS CAUTI
粪肠球菌中 EBPA-纤维原的相互作用
  • 批准号:
    8759401
  • 财政年份:
    2014
  • 资助金额:
    $ 34.2万
  • 项目类别:
EBPA-FIBROGEN INTERACTION IN ENTEROCOCCUS FAECALIS CAUTI
粪肠球菌中 EBPA-纤维原的相互作用
  • 批准号:
    8901925
  • 财政年份:
    2014
  • 资助金额:
    $ 34.2万
  • 项目类别:

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Segmented Filamentous Bacteria激活宿主免疫系统抑制其拮抗菌 Enterobacteriaceae维持菌群平衡及其机制研究
  • 批准号:
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    2024
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从肠道到大脑的细菌感觉转导来调节行为
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