Molecular Biology and Virulence of CTX Phage

可移动的遗传元件深刻地影响了细菌病原体的进化。许多 毒力和抗生素耐药性的决定因素由可移动的元件承载，如质粒和 能够水平传播的噬菌体。在当前的赠款周期中，我们探索了 关于CTXqj和CTXqj两个可移动遗传元件的分子生物学的几个基本问题 它对霍乱病原体的致病性和进化产生了深远的影响。弧菌 霍乱弧菌。解决这些目标已经产生了一些以前没有被认识到的观察结果 噬菌体基因调控机制及其生物学和进化研究的新进展 综合共轭要素(ICES)。此外，从这些研究中获得的知识被证明是 这对于我们研究导致海地霍乱暴发的霍乱弧菌菌株的来源至关重要。 在这个赠款周期中，我们还扩大了我们的工作范围，以包括对V的新方面的调查。 霍乱弧菌的生物学和致病性。特别是，我们开发了一种新的幼兔疾病模型 与人类霍乱非常相似。我们将利用这一模式和我们拥有的新的高吞吐量工具 为解决功绩延长期间的三个新目标而制定：1)评估空间和 霍乱弧菌感染期间基因表达的时间模式；2)鉴定和表征 霍乱弧菌传播的决定因素；以及3)霍乱弧菌的先天免疫反应 肠道定植。完成这些研究将为我们提供最全面的 任何细菌病原体在感染过程中的基因表达过程。此外，它还将增强我们的 了解霍乱弧菌致病和传播的潜在过程。最后，这些 研究应深入了解肠道内的先天免疫反应，调节 这对正常的肠道稳态和疾病都有深远的影响。总而言之，这些 研究将为创造新的抗菌剂和疫苗提供有价值的新知识。

Mobile genetic elements have profoundly influenced the evolution of bacterial pathogens. Many determinants of virulence and antibiotic resistance are borne by mobile elements, such as plasmids and bacteriophages, which are capable of horizontal transmission. During the current grant cycle, we explored several fundamental questions regarding the molecular biology of two mobile genetic elements, CTXqj and SXT, which have profoundly influenced the pathogenicity and evolution ofthe cholera pathogen. Vibrio cholerae. Addressing these aims has yielded observations that suggest previously unrecognized mechanisms of bacteriophage gene regulation and new insights regarding the biology and evolution of Integrative Conjugative Elements (ICEs). Furthermore, knowledge gained from these studies proved to be critical for our studies of the origin of the V. cholerae strain that gave rise to the cholera outbreak in Haiti. During this grant cycle, we also expanded the scope of our work to include investigation of new aspects of V. cholerae biology and pathogenicity. In particular, we developed a new infant rabbit model of disease that closely resembles human cholera. We will exploit this model and new high throughput tools we have developed to address three new aims during the MERIT extension period: 1) Assess the spatial and temporal patterns of V. cholerae gene expression during infection; 2) Identify and characterize the determinants of V. cholerae transmission; and 3) Characterize the innate immune response to V. cholerae intestinal colonization. Completion of these studies will provide the most comprehensive knowledge ofthe course of gene expression during infection for any bacterial pathogen. Additionally, it will enhance our understanding of the processes underlying V. cholerae pathogenicity and transmission. Finally, these studies should provide insight into the innate immune response within the intestinal tract, modulation of which has profound ramifications both for normal intestinal homeostasis and for disease. Collectively, these studies will yield valuable new knowledge for the creation of new antimicrobial agents and vaccines.