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

基本信息

  • 批准号:
    10452033
  • 负责人:
  • 金额:
    $ 23.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-01-05 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Microbial-derived Short Chain Fatty Acids (SCFAs) have emerged as important mediators of “Disease Tolerance,” a process that seeks to limit collateral damage to host tissues that accompanies immune responses. SCFAs are the principle end-products of the metabolism of the Gram-positive pathogen Streptococcus pyogenes which can cause several severe invasive diseases that are notoriously difficult to treat due to extensive and rapid tissue destruction that limits perfusion of antibiotics to the site of bacterial multiplication. For the most severe manifestations, in particular necrotizing fasciitis, lesions expand to involve additional tissue at a rapid rate that can approach several cm per hour. This necessitates multiple rounds of aggressive and disfiguring surgical interventions, including debridement, fasciotomy and even amputation of limbs and this lack of therapeutic options results in high mortality. An important gap in our treatment arsenal is the lack of therapies to mitigate tissue damage during severe invasive disease, which would improve the efficacy of antibiotic treatment to promote clearance of the infection. The goal of this study is to explore proof-of-principle that therapeutic manipulation of streptococcal pyruvate metabolism can provide a viable strategy for mitigation of tissue damage to improve treatment outcomes of severe, invasive S. pyogenes disease. This concept builds upon our preliminary data that suggests S. pyogenes employs its several alternative pathways for pyruvate reduction to actively manipulate the host’s “Disease Tolerance” response to promote its ability to infect diverse host niches. Disease tolerance is the process the host employs to balance pathogen growth against the collateral damage to host tissues that accompanies immune responses, known as Growth/Damage Balance. Through identification of host cells and relevant signaling pathways that control disease tolerance, a therapeutic approach that targets microbial metabolic and host cell signaling pathways can reduce damage to tissue to improve the ability of antibiotics to clear infections.
摘要

项目成果

期刊论文数量(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:
    10546470
  • 财政年份:
    2022
  • 资助金额:
    $ 23.63万
  • 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:
    $ 23.63万
  • 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:
    $ 23.63万
  • 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:
    $ 23.63万
  • 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:
    $ 23.63万
  • 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:
    $ 23.63万
  • 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:
    $ 23.63万
  • 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:
    $ 23.63万
  • 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:
    $ 23.63万
  • 项目类别:
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
  • 批准号:
    9174072
  • 财政年份:
    2007
  • 资助金额:
    $ 23.63万
  • 项目类别:

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