权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Host and microbial factors promoting synergistic mortality during polymicrobial intra-abdominal infections with Candida albicans and Staphylococcus aureus

白色念珠菌和金黄色葡萄球菌腹腔内多种微生物感染期间宿主和微生物因素促进协同死亡率

基本信息

批准号：
9984140
负责人：
Mairi C Noverr
金额：
$ 31.63万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-01 至 2020-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Polymicrobial infections involving fungal and bacterial pathogens are increasingly common among hospitalized patients. However, there is a paucity of research focused on studying polymicrobial infections. The fungal pathogen Candida albicans is the most common cause of invasive fungal infection and the third most common cause of nosocomial bloodstream infections in the US. Invasive fungal infections with C. albicans have devastatingly high mortality rates compared with bacterial infections. Bloodstream fungal infections, which are mostly monomicrobial, result in a 40% mortality rate. In contrast, intra-abdominal fungal infections (IAI), which are often polymicrobial involving both fungal and bacterial species, result in a 50-75% mortality rate, which far exceeds bacterial mono- or polymicrobial IAI mortality rates (20%). Fungal involvement also leads to increased rates of relapse and more severe disease scores. The mechanisms associated with this exacerbated mortality are currently unknown. The objective of this application is to characterize the host and microbial mechanism/s contributing to synergistic lethality during polymicrobial fungal-bacterial intra-abdominal infections (IAI). Our central hypothesis is that polymicrobial Candida-bacterial intra-abdominal infections promote synergistic effects on mortality by inducing a pathological inflammatory response locally and systemically (sepsis). Mechanistically, the response is induced by both microbe-microbe interactions and cross-kingdom stimulation of innate immune receptors. The first specific aim of this project is to test the hypothesis that specific eicosanoi signaling pathways (COX-1; PGE2; EP3) are required for pathological inflammation and lethality observed during polymicrobial fungal-bacterial IAI. The second specific aim is to test the hypothesis that PRR signaling from both fungal and bacterial pathogens is required for enhanced eicosanoid production, inflammation, and lethality observed during polymicrobial IAI. The third specific aim is to test the hypothesis that C. albicans promotion of bacterial toxin production augments inflammation and mortality during fungal-bacterial polymicrobial IAI.

描述（由申请人提供）：涉及真菌和细菌病原体的多种微生物感染在住院患者中越来越常见。然而，专注于研究多种微生物感染的研究很少。真菌病原体白色念珠菌是侵袭性真菌感染的最常见原因，也是美国医院血流感染的第三大常见原因。与细菌感染相比，白色念珠菌侵袭性真菌感染的死亡率极高。血液真菌感染大多是单一微生物，导致 40% 的死亡率。相比之下，腹内真菌感染 (IAI) 通常是涉及真菌和细菌物种的多种微生物，导致 50-75% 的死亡率，远远超过细菌单一或多种微生物 IAI 死亡率 (20%)。真菌参与还会导致复发率增加和疾病评分更严重。目前尚不清楚与这种死亡率上升相关的机制。本申请的目的是表征多种微生物真菌-细菌腹内感染 (IAI) 期间导致协同致死的宿主和微生物机制。我们的中心假设是，腹腔内多种微生物念珠菌感染通过诱导局部和全身病理性炎症反应（脓毒症）来促进死亡率的协同效应。从机制上讲，这种反应是由微生物与微生物之间的相互作用和先天免疫受体的跨界刺激引起的。该项目的第一个具体目标是检验这样的假设：特定的二十烷醇信号通路（COX-1；PGE2；EP3）对于多种微生物真菌-细菌 IAI 期间观察到的病理性炎症和致死性是必需的。第二个具体目标是检验这样的假设：来自真菌和细菌病原体的 PRR 信号对于增强类二十烷酸的产生、炎症和在多微生物 IAI 期间观察到的致死率是必需的。第三个具体目标是检验白色念珠菌促进细菌毒素产生会增加真菌-细菌多微生物 IAI 期间的炎症和死亡率的假设。