课题基金 / 基金详情

Candida Albicans Gastrointestinal Colonization and Dissemination

Candida Albicans Gastrointestinal Colonization and Dissemination
白色念珠菌胃肠道定植和传播
批准号:
9761967
负责人:
ANDREW Y KOH
金额:
$40.5万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-28 至 2021-08-31

项目摘要

项目成果

ANDREW Y KOH的其他基金

相似基金

相关文献

中文摘要
翻译
侵袭性疾病需要白色念珠菌(CA)定植。成年小鼠对CA有抗性
英文摘要
Candida albicans (CA) colonization is required for invasive disease. Adult mice are resistant to CA gastrointestinal (GI) colonization. We have identified two genetically distinct anaerobic commensal bacteria that can individually maintain CA colonization resistance in germ-free mice. These anaerobic commensals induce host immune effectors (transcription factor, HIF1-α, and antimicrobial peptide, CRAMP/LL-37) that significantly decrease CA GI colonization. By pharmacologically inducing both HIF1-α and CRAMP, we were able to significantly reduce CA colonization and reduce mortality from CA dissemination by 50%. Interestingly, the anaerobic bacteria that can expel CA from the gut share the ability to produce short-chain fatty acids (SCFAs). SCFAS have been shown to have numerous immunomodulatory properties. Therefore, my central hypothesis is that SCFAs produced by gut commensal anaerobic bacteria are necessary to maintain CA colonization resistance. This work will involve two specific aims. First, I will determine whether SCFAs are necessary for CA colonization resistance. I will evaluate whether commensal anaerobe Bacteroides thetaiotamicron mutants unable to produce SCFAs or SCFAs alone can reduce CA colonization. I predict that SCFAs are necessary for maintaining CA colonization resistance. Second, I will determine if HIF-1α and/or CRAMP are necessary for SCFA-induced GI colonization reduction. I will evaluate whether SCFAs can promote CA clearance in cultured human and mouse gut epithelial cells and CA colonization reduction in Hif1a and Cramp knockout mice. I predict that HIF1-α and CRAMP are necessary for maintaining CA colonization resistance. Given the high morbidity and mortality associated with invasive fungal infections, the limited arsenal of antifungal antibiotics, and the continuing emergence of antibiotic resistant strains, new approaches to treating and preventing invasive fungal infections in patients are desperately needed. Using natural occurring anaerobic bacterial metabolites (SCFAs) to boost GI mucosal immune effectors to reduce fungal colonization and ultimately decrease dissemination could represent paradigm shift in the way we prevent/treat fungal infections in patients. These studies will lay the groundwork for the following innovations: 1) a novel mechanism by which SCFAs activate gut immune defenses to maintain CA colonization resistance; 2) a novel approach (SCFAs) to inhibit CA dissemination; and 3) a novel approach to preventing fungal infections in patients. Together, these studies should lead to fundamental insights into bacterial/fungal interactions within the intestinal tract and will provide new perspectives in combating invasive fungal disease in the human host.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A Novel Bacterially-derived Product to Enhance Immunity and Response to Immune Checkpoint Therapy
  • 批准号:
    10482027
  • 项目类别:
  • 资助金额:
    $28.92万
  • 财政年份:
    2022
  • 负责人:
    ANDREW Y KOH
  • 依托单位:
Mentoring Patient Oriented Research in the Microbiome of Cancer and Stem Cell Transplant Patients
  • 批准号:
    10593178
  • 项目类别:
  • 资助金额:
    $11.69万
  • 财政年份:
    2020
  • 负责人:
    ANDREW Y KOH
  • 依托单位:
Mentoring Patient Oriented Research in the Microbiome of Cancer and Stem Cell Transplant Patients
  • 批准号:
    10370367
  • 项目类别:
  • 资助金额:
    $11.84万
  • 财政年份:
    2020
  • 负责人:
    ANDREW Y KOH
  • 依托单位:
Candida Albicans Gastrointestinal Colonization and Dissemination
  • 批准号:
    9360089
  • 项目类别:
  • 资助金额:
    $40.5万
  • 财政年份:
    2016
  • 负责人:
    ANDREW Y KOH
  • 依托单位:
海外基金