Factors leading to enhanced Pseudomonas aeruginosa infection in diabetic wounds

导致糖尿病伤口铜绿假单胞菌感染增强的因素

基本信息

  • 批准号:
    9355169
  • 负责人:
  • 金额:
    $ 34.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-20 至 2021-07-31
  • 项目状态:
    已结题

项目摘要

Foot ulcers are one of the leading causes of hospitalization for people with diabetes in the developed world and a major morbidity associated with diabetes leading to pain, suffering, and a poor quality of life for patients. 25.8 million patients with diabetes in US alone develop foot ulcers at some point in their lives, costing approximately 25 billion dollars in care annually and accounting for 67% of all lower extremity amputations in the US. Bacterial infection has been long recognized as a major impediment to wound healing in diabetic ulcers. A shift in the microbiome toward pathogenic bacteria, such as Pseudomonas aeruginosa occurs in diabetic ulcers and correlates with a poor healing prognosis. The underlying reasons for the inability of diabetic wounds to fight off bacterial infection and the reasons for the microbiome shift toward pathogenic bacteria remain poorly understood. Based on our preliminary data, our central hypothesis is that inadequate neutrophil infiltration early after injury in diabetic wound-- due to impaired neutrophil chemotactic response through the formylated peptide receptor (FPR) -- leads to reduced TLR signaling, reduced inflammatory responses, and reduced pathogen-specific AMP expression, rendering diabetic wound vulnerable to infection with pathogenic bacteria, which further exacerbate diabetic wound, driving it toward hyper-inflammatory and chronic state. In this proposal, we will: (Aim 1) determine the molecular mechanisms that underlie the impaired neutrophil response in diabetic wound; (Aim 2) assess the adverse impact of delayed neutrophil response on signaling through pattern recognition receptors (PRRs); and (Aim 3) assess the adverse impact of delayed neutrophil response on antimicrobial peptides (AMPs) productions, particularly the pathogen-specific AMPs that render diabetic wounds vulnerable to colonization and microbiome shift toward Pseudomonas aeruginosa. We will also evaluate the therapeutic potential of pro-inflammatory chemokines and Toll-like receptor ligands to restore antimicrobial defenses and stimulate healing by jumpstarting the neutrophil response in diabetic wounds early after injury.
足部溃疡是发达国家糖尿病患者住院的主要原因之一, 与糖尿病相关的主要发病率,导致患者疼痛、痛苦和生活质量差。25.8 仅在美国,就有100万糖尿病患者在其生命的某个阶段发生足部溃疡, 每年花费10亿美元,占美国所有下肢截肢手术的67%。细菌 感染长期以来被认为是糖尿病溃疡伤口愈合的主要障碍。的转变 微生物组对致病菌如铜绿假单胞菌的作用发生在糖尿病溃疡中, 与不良的愈合预后相关。糖尿病伤口无法击退的根本原因 细菌感染和微生物组向致病菌转变的原因仍然知之甚少。 根据我们的初步数据,我们的中心假设是,在创伤后早期中性粒细胞浸润不足, 糖尿病伤口--由于通过甲酰化肽受体(FPR)的中性粒细胞趋化反应受损 --导致TLR信号传导减少,炎症反应减少,病原体特异性AMP减少 表达,使糖尿病伤口易受病原菌感染,这进一步加剧了 糖尿病伤口,将其推向高度炎症和慢性状态。在本建议中,我们将:(目标1)确定 糖尿病伤口中性粒细胞反应受损的分子机制;(目的2)评估 延迟的中性粒细胞应答对通过模式识别受体(PRR)的信号传导的不利影响;以及 (Aim 3)评估延迟中性粒细胞应答对抗菌肽(AMP)产生的不利影响, 特别是病原体特异性AMP,其使糖尿病伤口易于定植和微生物组 转向铜绿假单胞菌。我们还将评估促炎性细胞因子的治疗潜力。 趋化因子和Toll样受体配体,以恢复抗微生物防御并通过跳跃启动刺激愈合 糖尿病伤口损伤后早期的中性粒细胞反应。

项目成果

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SASHA H SHAFIKHANI其他文献

SASHA H SHAFIKHANI的其他文献

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{{ truncateString('SASHA H SHAFIKHANI', 18)}}的其他基金

Role of immune system in prophylaxis antibiotic's surgical site infection control
免疫系统在预防性抗生素控制手术部位感染中的作用
  • 批准号:
    10672940
  • 财政年份:
    2020
  • 资助金额:
    $ 34.88万
  • 项目类别:
Role of immune system in prophylaxis antibiotic's surgical site infection control
免疫系统在预防性抗生素控制手术部位感染中的作用
  • 批准号:
    10115388
  • 财政年份:
    2020
  • 资助金额:
    $ 34.88万
  • 项目类别:
Role of immune system in prophylaxis antibiotic's surgical site infection control
免疫系统在预防性抗生素控制手术部位感染中的作用
  • 批准号:
    10462642
  • 财政年份:
    2020
  • 资助金额:
    $ 34.88万
  • 项目类别:
Role of immune system in prophylaxis antibiotic's surgical site infection control
免疫系统在预防性抗生素控制手术部位感染中的作用
  • 批准号:
    10269052
  • 财政年份:
    2020
  • 资助金额:
    $ 34.88万
  • 项目类别:
Factors Leading to Enhanced Pseudomonas Aeruginosa Infection in Diabetic Wounds
导致糖尿病伤口铜绿假单胞菌感染增强的因素
  • 批准号:
    9974298
  • 财政年份:
    2016
  • 资助金额:
    $ 34.88万
  • 项目类别:
Molecular dissection of Pseudomonas aeruginosa Exotoxin T virulence functions
铜绿假单胞菌外毒素T毒力功能的分子解析
  • 批准号:
    8808367
  • 财政年份:
    2015
  • 资助金额:
    $ 34.88万
  • 项目类别:
Factors leading to enhanced Pseudomonas aeruginosa infection in diabetic wounds
导致糖尿病伤口铜绿假单胞菌感染增强的因素
  • 批准号:
    9131855
  • 财政年份:
    2015
  • 资助金额:
    $ 34.88万
  • 项目类别:
Molecular dissection of Pseudomonas aeruginosa Exotoxin T virulence functions
铜绿假单胞菌外毒素T毒力功能的分子解析
  • 批准号:
    9052701
  • 财政年份:
    2015
  • 资助金额:
    $ 34.88万
  • 项目类别:
Pseudomonas aeruginosa-induced host cell pathogenesis
铜绿假单胞菌诱导的宿主细胞发病机制
  • 批准号:
    6583942
  • 财政年份:
    2003
  • 资助金额:
    $ 34.88万
  • 项目类别:
Pseudomonas aeruginosa-induced host cell pathogenesis
铜绿假单胞菌诱导的宿主细胞发病机制
  • 批准号:
    6877748
  • 财政年份:
    2003
  • 资助金额:
    $ 34.88万
  • 项目类别:

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