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。有一个正在进行的研究努力，以确定和功能描述这些因素，以了解细菌病原体的行为。这项研究对于开发明智的治疗方法也至关重要，这些治疗方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，世界范围内的水产养殖受到抗生素多重耐药病原体的影响。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研究一种主要的鱼类病原体——沙门氏菌气单胞菌。我们将继续探索其基因组不稳定性中众多可移动遗传元件的参与，从而导致在应激条件下毒性因子的丧失。我们还将在新的水生控制2级（AQC2）体内设施中开展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和一般病原体的毒力，包括它与多个宿主的相互作用。基于我们正在努力了解沙门氏菌的致病基础和本提案中设定的目标，我们有信心在相对短期内可以针对这种细菌进行具体治疗。

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.