Salmonella polymicrobial interactions

描述(申请人提供)：沙门氏菌多菌相互作用摘要正常的微生物区系为宿主提供必要的营养和维生素，也使病原微生物很难定植。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所起的作用还没有得到很好的研究。我们已经确定沙门氏菌编码一个名为SdiA的LuxR同源物，它可以检测宿主中其他病原菌的信号分子。到目前为止，我们已经确定沙门氏菌可以在乌龟身上检测到嗜水气单胞菌，在小鼠和猪身上检测到耶尔森氏菌。沙门氏菌在猪体内检测耶尔森氏菌信号分子的能力导致了沙门氏菌脱落的大幅增加。在另一项研究中，最近观察到感染了小肠结肠炎耶尔森菌的猪被肠道沙门氏菌定植的风险增加。鉴于沙门氏菌是世界上最重要的病原体之一，重要的是确定导致这种生物传播的参数。在这项工作中，将确定耶尔森氏菌感染在多大程度上增加了沙门氏菌在宿主上的定植能力并将其从宿主中排出。我们将检验这样的假设，即沙门氏菌的感染量、沙门氏菌的脱落量和沙门氏菌脱落物的持久性以一种取决于沙门氏菌检测耶尔森氏菌合成的AHLS的能力的方式改变。单个sdiA调节子成员在这些表型中的作用将被确定。此外，基于阵列的转座子筛选将用于识别利用联合感染所需的新的沙门氏菌基因。这些基因将被解析为依赖于sdiA和不依赖于sdiA的基因，依赖于sdiA的基因将被进一步分类，以确定它们是sdiA调节子的新成员还是与sdiA协同作用的基因。关联性。宿主的正常微生物区系在预防细菌感染中起着非常重要的作用。病原体绕过或竞争正常微生物区系的机制在很大程度上尚不清楚。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区系相互作用的机制将有助于深入了解病原体的寄主范围以及疾病和流行病的生态。这将有助于抗生素和益生菌的合理设计和使用。

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.