Investigating bacterial virulence of aquatic pathogens using multiple host-pathogen models

毒力被定义为细菌病原体通过产生病原体在宿主中入侵、繁殖和茁壮成长所必需的因子来伤害宿主的能力。有一个正在进行的研究工作，以确定和功能描述这些因素，以了解细菌病原体的行为。这项研究对于开发可用作抗生素替代品的明智治疗方法也至关重要，抗生素对感染人类和动物的各种病原体的有效性越来越低。例如，水产养殖在世界范围内受到抗生素多重耐药性病原体的出现的困扰。我的研究计划的长期目标是确定水生病原体产生的毒力因子的分子基础，以及抑制或调节它们的方法，以预防或治疗细菌感染。 在接下来的五年里，我的研究计划将继续集中在主要鱼类病原体杀鲑鱼气单胞菌的研究上。我们将继续探讨参与的许多移动的遗传因素在其基因组的不稳定性，导致损失的毒力因子，以应对压力的条件。我们还将开展A.在一个新的水隔离2级（AQC2）体内设施中，用原生动物和鱼类对杀鲑藻菌进行了研究，为过去不可行的实验打开了大门。我提出的研究计划将有助于更好地了解A.杀鲑鱼的病原体，包括其与多种宿主的相互作用。基于我们对A.鉴于杀鲑素的作用及本建议书所载的目标，我们有信心可在相对短期内采取具体措施对付这种细菌。

Virulence is defined as the ability of a bacterial pathogen to injure a host by producing factors that are essential for the pathogen to invade, multiply and thrive in the host. There is an ongoing research effort to identify and functionally describe these factors in order to understand the behavior of bacterial pathogens. This research is also crucial for the development of judicious treatments that can be used as alternatives to antibiotics which are less and less effective against a wide variety of pathogens infecting humans, but also animals. For example, the aquaculture is afflicted worldwide by the emergence of antibiotic multi-resistant pathogens. The long-term objective of my research program is to identify the molecular basis of the virulence factors produced by aquatic pathogens as well as ways to inhibit or modulate them in order to prevent or treat bacterial infections. Over the next five years, my research program will continue to concentrate on the study of Aeromonas salmonicida, a major fish pathogen. We will continue to explore the involvement of the numerous mobile genetic elements in the instability of its genome leading to loss of virulence factors in response to stressful conditions. We will also initiate research on the interaction of A. salmonicida with protozoa and fish in a new AQuatic Containment level 2 (AQC2) in vivo facilities, opening the door to experiments not feasible in the past. My proposed research program will provide a better understanding of the virulence of A. salmonicida and of pathogens in general including its interactions with multiple hosts. Based on our ongoing effort to understand the pathogenic basis of A. salmonicida and the objectives set out in this proposal, we are confident that concrete treatments against this bacterium will be possible on a relative short term.