Oral Epithelial Cells, Candida and PMN Activation

口腔上皮细胞、念珠菌和 PMN 激活

基本信息

项目摘要

PROJECT SUMMARY The oral mucosal microbiota is a complex ecosystem primarily represented by bacteria and fungi. Most oropharyngeal fungal infections are caused by the genus Candida and are assumed to result from an overgrowth of indigenous species, primarily C. albicans. C. albicans is a commensal colonizer of the oral mucosa in humans, but is also responsible for infections afflicting immunocompromised hosts. Persistent oropharyngeal thrush is refractory to most antifungals and a significant clinical problem in pharmacologically immunosuppressed patients. Corticosteroid-induced and chemotherapy-induced immunosuppression, are two main risk factors for oropharyngeal candidiasis in humans. C. albicans also causes fungemia, a serious consequence of cancer cytotoxic chemotherapy, which is thought to develop from fungal translocation through compromised mucosal barriers. Changes in endogenous bacterial population size or composition and in the host environment can transform fungal commensals into pathobionts. Work in our previous funding cycle established a synergistic relationship of mitis group streptococci with C. albicans in the pathogenesis of oral candidiasis. We identified mechanisms of synergy which involved both a direct effect on fungal virulence gene expression and a modification of host responses. In this project we will build on our ongoing studies examining the interplay of the resident oral mucosal bacterial microbiota and C. albicans. We will use mouse models of commensal colonization or mucosal infection to interrogate oral bacterial microbiome parameters that promote C. albicans virulence. In aim 1 we will characterize dysbiotic changes in mucosa-associated bacterial communities in oropharyngeal candidiasis, using our established mouse models of cortisone- and chemotherapy-induced immunosuppression. We will then test the hypothesis that certain endogenous bacterial species isolated from dysbiotic states can exhibit pathogenic synergy with C. albicans. In aim 2 we will define the regulatory mechanisms of fungal-bacterial mucosal biofilm growth in each immunosuppression state. Finally, in aim 3 we will examine the role of the dysbiotic communities and host response in mucosal barrier breach and bloodstream dissemination by C. albicans. The proposed studies have the potential to lead to a paradigm shift in how clinicians and scientists view the microbiome changes characterizing mucosal Candida infections. This project will identify certain oral bacteria as new, clinically relevant mediators of invasive fungal infections thus providing justification for the combined use of antifungal and anti-bacterial treatments in at risk patients. A better understanding of the relationship between fungi and the oral microbiome could also result in new biomarkers of infection risk or identification of probiotic commensals that could lower the likelihood of invasive mucosal candidiasis in high-risk populations such as patients undergoing intensive cancer chemotherapy.
项目总结

项目成果

期刊论文数量(52)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Streptococcal co-infection augments Candida pathogenicity by amplifying the mucosal inflammatory response.
  • DOI:
    10.1111/cmi.12216
  • 发表时间:
    2014-02
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Xu H;Sobue T;Thompson A;Xie Z;Poon K;Ricker A;Cervantes J;Diaz PI;Dongari-Bagtzoglou A
  • 通讯作者:
    Dongari-Bagtzoglou A
Chemotherapy-induced oral mucositis and associated infections in a novel organotypic model.
  • DOI:
    10.1111/omi.12214
  • 发表时间:
    2018-06
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Sobue T;Bertolini M;Thompson A;Peterson DE;Diaz PI;Dongari-Bagtzoglou A
  • 通讯作者:
    Dongari-Bagtzoglou A
Host cell invasion and virulence mediated by Candida albicans Ssa1.
  • DOI:
    10.1371/journal.ppat.1001181
  • 发表时间:
    2010-11-11
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Sun JN;Solis NV;Phan QT;Bajwa JS;Kashleva H;Thompson A;Liu Y;Dongari-Bagtzoglou A;Edgerton M;Filler SG
  • 通讯作者:
    Filler SG
Characterization of mucosal Candida albicans biofilms.
粘膜念珠菌生物膜的表征。
  • DOI:
    10.1371/journal.pone.0007967
  • 发表时间:
    2009-11-24
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Dongari-Bagtzoglou A;Kashleva H;Dwivedi P;Diaz P;Vasilakos J
  • 通讯作者:
    Vasilakos J
Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.
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Anna I Dongari-Bagtzoglou其他文献

Anna I Dongari-Bagtzoglou的其他文献

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{{ truncateString('Anna I Dongari-Bagtzoglou', 18)}}的其他基金

Control of heterogeneous microbial communities using model-based multi-objective optimization
使用基于模型的多目标优化控制异质微生物群落
  • 批准号:
    10268262
  • 财政年份:
    2018
  • 资助金额:
    $ 58.52万
  • 项目类别:
Control of heterogeneous microbial communities using model-based multi-objective optimization
使用基于模型的多目标优化控制异质微生物群落
  • 批准号:
    10267334
  • 财政年份:
    2018
  • 资助金额:
    $ 58.52万
  • 项目类别:
Model of chemotherapy-induced mucositis
化疗引起的粘膜炎模型
  • 批准号:
    8871565
  • 财政年份:
    2014
  • 资助金额:
    $ 58.52万
  • 项目类别:
Model of chemotherapy-induced mucositis
化疗引起的粘膜炎模型
  • 批准号:
    8770223
  • 财政年份:
    2014
  • 资助金额:
    $ 58.52万
  • 项目类别:
Oral Epithelial Cells, Candida and PMN Activation
口腔上皮细胞、念珠菌和 PMN 激活
  • 批准号:
    7932529
  • 财政年份:
    2009
  • 资助金额:
    $ 58.52万
  • 项目类别:
ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS
移植患者的口腔感染和炎症
  • 批准号:
    7719123
  • 财政年份:
    2008
  • 资助金额:
    $ 58.52万
  • 项目类别:
ORAL CANDIDA
口腔念珠菌
  • 批准号:
    7719112
  • 财政年份:
    2008
  • 资助金额:
    $ 58.52万
  • 项目类别:
ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS
移植患者的口腔感染和炎症
  • 批准号:
    7607625
  • 财政年份:
    2007
  • 资助金额:
    $ 58.52万
  • 项目类别:
ORAL CANDIDA
口腔念珠菌
  • 批准号:
    7607610
  • 财政年份:
    2007
  • 资助金额:
    $ 58.52万
  • 项目类别:
ORAL INFECTION AND INFLAMMATION IN TRANSPLANT PATIENTS
移植患者的口腔感染和炎症
  • 批准号:
    7377365
  • 财政年份:
    2006
  • 资助金额:
    $ 58.52万
  • 项目类别:

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New technologies for targeted delivery of anti-bacterial agents
抗菌药物靶向递送新技术
  • 批准号:
    1654774
  • 财政年份:
    2015
  • 资助金额:
    $ 58.52万
  • 项目类别:
    Studentship
Targeting bacterial phosphatases for novel anti-bacterial agents.
针对细菌磷酸酶的新型抗菌剂。
  • 批准号:
    8416313
  • 财政年份:
    2012
  • 资助金额:
    $ 58.52万
  • 项目类别:
Targeting bacterial phosphatases for novel anti-bacterial agents.
针对细菌磷酸酶的新型抗菌剂。
  • 批准号:
    8298885
  • 财政年份:
    2012
  • 资助金额:
    $ 58.52万
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