Molecular Biology and Virulence of CTX Phage

移动的遗传元件深刻地影响了细菌病原体的进化。许多 毒力和抗生素抗性的决定子由移动的元件携带，例如质粒和 噬菌体，能够水平传播。在当前的赠款周期中，我们探索了 关于两个移动的遗传元件CTXqj和 SXT对霍乱病原体的致病性和进化产生了深远的影响。弧菌 胆汁。为实现这些目标，人们提出了一些以前没有认识到的意见， 噬菌体基因调控的机制和关于噬菌体的生物学和进化的新见解 整合共轭元素（ICE）。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爆发的霍乱弧菌菌株的起源至关重要。 在这个资助周期中，我们还扩大了我们的工作范围，包括对V的新方面的调查。 霍乱生物学和致病性。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种模式和新的高通量工具，我们有 在MERIT延长期内，制定了三个新目标：1）评估空间和 感染期间霍乱弧菌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;和3）表征对霍乱弧菌的先天免疫应答 肠道定植完成这些研究将提供最全面的知识， 任何细菌病原体感染期间的基因表达过程。此外，它还将增强我们的 了解霍乱弧菌致病性和传播的基本过程。最后这些 研究应该提供对肠道内先天性免疫反应的深入了解， 这对正常的肠道内环境平衡和疾病都有深远的影响。总的来说，这些 这些研究将为创造新的抗菌剂和疫苗提供宝贵的新知识。

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.