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对病原体入侵、繁殖和在宿主中茁壮成长所必需的因子来伤害宿主的能力。为了了解细菌病原体的行为，正在进行一项识别和功能描述这些因素的研究工作。这项研究对于开发明智的治疗方法也至关重要，这些疗法可以用作抗生素的替代品，抗生素对感染人类和动物的各种病原体的效果越来越差。例如，全球水产养殖业受到抗生素多重耐药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对沙门氏气单胞菌的研究上，这是一种主要的鱼类病原体。我们将继续探索众多可移动的遗传元件参与其基因组的不稳定，导致毒力因子在应激条件下的丧失。我们还将在一个新的水生二级(AQC2)体内设施中启动关于沙门氏菌与原生动物和鱼类相互作用的研究，为过去不可行的实验打开大门。我提出的研究计划将更好地了解沙门氏菌的毒力和病原体的一般情况，包括它与多个宿主的相互作用。基于我们正在进行的了解沙门氏菌致病基础的努力以及本提案中提出的目标，我们相信，在相对较短的时间内，针对这种细菌的具体治疗是可能的。

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.