Mechanisms of Enteric Burkholderia psuedomallei infection

肠道假鼻疽伯克霍尔德氏菌感染的机制

基本信息

批准号：
8028304
负责人：
Steven W. Dow
金额：
$ 18.07万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2012-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Burkholderia pseudomallei (Bp) is a Gram-negative bacterial pathogen that can cause a variety of difficult-to-treat infections in humans ranging from acute sepsis to chronic abscesses. While Bp is endemic in Southeast Asia and northern Australia, infections are now being diagnosed with increasing frequency around the world, including in Central and South America. Therefore, it is likely that Bp infections will soon be identified in the U.S. Though infection with Bp was previously thought to occur by inhalation or skin inoculation, our new studies indicate that Bp is actually a primary enteric pathogen, which can readily establish acute or persistent GI tract infection following oral inoculation in mouse models. However, at present essentially nothing is known regarding the pathogenesis of enteric infection with Bp. Therefore, the studies proposed here are intended to fill a critical void in our understanding of pathogenesis of infection with this important and emerging bacterial pathogen. First, we will use the mouse infection model of Bp infection to determine whether most or all strains of Bp can establish enteric infection and to identify virulent and avirulent isolates. Second, we will use the model to define the role of the intestine as a reservoir for Bp infection and to identify cells in the GI tract where the organism is maintained during chronic infection. Last, we will investigate how Bp is disseminated to other organs during chronic enteric infection. The information generated in these studies will substantially alter our view of Bp as a pathogen and also lead to a reassessment of the risks posed by oral Bp infection. PUBLIC HEALTH RELEVANCE: Burkholderia pseudomallei is an important and dangerous bacterial pathogen that appears in recent years to be spreading around the world, including Central and South America. This organism is particularly dangerous because it is able to survive for years in soil and water, is very resistant to most antibiotics, and can cause rapidly fatal infections in humans. Previously it was assumed that the organism was contracted only by inhalation or skin injury, but our new data indicate that B. pseudomallei is also very infectious orally and causes chronic intestinal infection with fecal shedding. We will therefore study the mechanisms that allow B. pseudomallei to infect the intestinal tract, using mouse models of infection.

描述（由申请人提供）：类鼻疽伯克霍尔德氏菌（Bp）是一种革兰氏阴性细菌病原体，可引起人类多种难以治疗的感染，从急性败血症到慢性脓肿。虽然 Bp 在东南亚和澳大利亚北部流行，但现在世界各地（包括中美洲和南美洲）的感染诊断频率不断增加。因此，Bp 感染很可能很快就会在美国被发现。虽然 Bp 感染以前被认为是通过吸入或皮肤接种而发生的，但我们的新研究表明，Bp 实际上是一种主要的肠道病原体，很容易形成急性或持续性感染。小鼠模型口服接种后胃肠道感染。然而，目前对于 Bp 肠道感染的发病机制基本上一无所知。因此，这里提出的研究旨在填补我们对这种重要的新兴细菌病原体感染发病机制的理解中的一个关键空白。首先，我们将使用 Bp 感染的小鼠感染模型来确定大多数或所有 Bp 菌株是否可以建立肠道感染，并鉴定强毒力和无毒力分离株。其次，我们将使用该模型来定义肠道作为 Bp 感染储存库的作用，并识别胃肠道中的细胞，在慢性感染期间，微生物在胃肠道中得以维持。最后，我们将研究慢性肠道感染期间 Bp 如何传播到其他器官。这些研究中产生的信息将极大地改变我们对 Bp 作为病原体的看法，并导致人们重新评估口腔 Bp 感染所带来的风险。公共卫生相关性：鼻疽伯克霍尔德氏菌是一种重要且危险的细菌病原体，近年来似乎在世界各地传播，包括中美洲和南美洲。这种生物体特别危险，因为它能够在土壤和水中存活多年，对大多数抗生素具有很强的抵抗力，并且可以迅速引起人类致命的感染。此前人们认为该生物体仅通过吸入或皮肤损伤而感染，但我们的新数据表明，类鼻疽伯克氏菌经口传染性也很强，可导致慢性肠道感染并伴有粪便排出。因此，我们将使用小鼠感染模型来研究类鼻疽伯克氏菌感染肠道的机制。