Salmonella polymicrobial interactions

描述（由申请人提供）：沙门氏菌多微生物相互作用摘要正常的微生物群为宿主提供必需的营养素和维生素，也使病原微生物很难定殖。众所周知，某些病毒感染可促进继发性细菌感染。然而，细菌在促进其他细菌感染中的作用尚未得到充分研究。我们已经确定沙门氏菌编码一种名为SdiA的LuxR同源物，该同源物可以检测宿主中其他致病菌的信号分子。到目前为止，我们已经确定沙门氏菌可以检测海龟中的气单胞菌和小鼠和猪中的小肠结肠炎耶尔森氏菌。沙门氏菌检测猪体内耶尔森氏菌信号分子的能力导致沙门氏菌脱落的大量增加。在一项单独的研究中，最近观察到感染小肠结肠炎耶尔森氏菌的猪被肠道沙门氏菌定殖的风险增加。鉴于沙门氏菌是世界上最重要的病原体之一，重要的是要确定导致这种生物体传播的参数。在这项工作中，将确定耶尔森氏菌感染增加沙门氏菌定植宿主并从宿主脱落的能力的程度。我们将测试的假设，沙门氏菌的感染剂量，沙门氏菌脱落的量，沙门氏菌脱落的持久性改变的方式依赖于沙门氏菌检测由耶尔森氏菌合成的AHLs的能力。将确定单个sdiA调节子成员在这些表型中的每一种中的作用。此外，基于阵列的转座子筛选将用于鉴定利用合并感染所需的新型沙门氏菌基因。这些基因将被解析成sdiA依赖性和sdiA非依赖性组，其中sdiA依赖性组被进一步分类为它们是sdiA调节子的新成员还是与sdiA协同作用的基因。本案无关宿主的正常微生物群在预防细菌感染方面起着非常重要的作用。病原体绕过或胜过正常微生物群的机制在很大程度上是未知的。在这个提议中，我们假设一种方法是利用另一种病原体的成功。了解病原体相互作用以及与正常微生物群相互作用的机制将有助于深入了解病原体宿主范围以及疾病和流行病的生态学。这将有助于合理设计和使用抗生素和益生菌。

DESCRIPTION (provided by applicant): Salmonella polymicrobial interactions Abstract The normal microbiota provide essential nutrients and vitamins to the host and also make it very difficult for pathogenic microbes to colonize. It is well known that certain viral infections can facilitate secondary bacterial infections. However, the role that bacteria play in facilitating other bacterial infections is not well studied. We have determined that Salmonella encodes a LuxR homolog named SdiA that can detect the signaling molecules of other pathogenic bacteria in the host. To date, we have determined that Salmonella can detect Aeromonas hydrophila in turtles and Yersinia enterocolitica in mice and pigs. The ability of Salmonella to detect the signaling molecules of Yersinia in pigs led to a large increase in Salmonella shedding. In a separate study it was recently observed that swine infected with Yersinia enterocolitica are at increased risk to be colonized with Salmonella enterica. Given that Salmonella is one of the world's most significant pathogens, it is important to determine the parameters that lead to transmission of this organism. In this work, the extent to which a Yersinia infection increases the ability of Salmonella to colonize a host and be shed from that host will be determined. We will test the hypotheses that the infectious dose for Salmonella, the amount of Salmonella shed, and the persistence of Salmonella shedding are altered in a manner dependent upon the ability of Salmonella to detect the AHLs synthesized by Yersinia. The role of individual sdiA regulon members in each of these phenotypes will be determined. Additionally, array-based transposon screening will be used to identify novel Salmonella genes required to take advantage of coinfections. These genes will be parsed into sdiA- dependent and -independent groups, with the sdiA-dependent group being further categorized as to whether they are new members of the sdiA regulon or genes that act synergistically with sdiA. Relevance. The normal microbiota of the host play a very important role in preventing bacterial infections. The mechanisms by which pathogens circumvent or outcompete the normal microbiota are largely unknown. In this proposal we hypothesize that one method is to take advantage of another pathogen's success. Understanding the mechanisms by which pathogens interact with each other and with the normal microbiota will provide insights into pathogen host range and the ecology of disease and epidemics. This will facilitate the rational design and use of antibiotics and probiotics.