Grant: Discovery Grants Program - Individual

Infection initiates a dynamic cascade of events that culminates in disease or pathogen clearance by the host immune system. A global understanding of the molecular network of bacterial-fish interactions is essential for the development of effective treatments, vaccination, and eradication plans. Fish are the most diverse vertebrates on earth, as well their immune system. Although teleosts are very diverse, they have common bacterial infectious diseases. First described in the 19th century, Aeromonas salmonicida subsp salmonicida is one of the oldest known fish pathogens, endemic worldwide in both fresh and marine water, and the etiological agent of furunculosis. Here, I propose to investigate serval aspects of A. salmonicida pathogenesis and physiology. A. salmonicida can infect different hosts, including Atlantic cod (Gadus morhua). In contrast to Atlantic salmon (Salmo salar), G. morhua lack the MHC-II and the mechanisms by which G. morhua effectively fights bacterial infections are not understood. I will study the A. salmonicida gene expression during intracellular infection and how S. salar and G. morhua respond to the same pathogen. Role of specific A. salmonicida genes on virulence and fish immune response will be studied. A pathogenic lifestyle requires tight control of virulence gene expression. Non-coding RNAs (ncRNAs) post-transcriptionally regulate multiple processes, including pathogenesis. I will study the role of predicted ncRNAs on A. salmonicida physiology, virulence, and immune response in vivo. The A. salmonicida chromosome is susceptible to endogenous mutagenesis caused by thermal inducible insertion sequences (ISs). Regulation of A. salmonicida ISs is unknown. Here, I will study the role of cold-shock proteins (Csp) on A. salmonicida endogenous mutagenesis and virulence. The discovery of regulatory networks between A. salmonicida and S. salar, and G. morhua hosts, and how G. morhua fight bacterial infections in the absence of MHC-II will be the fundamental contributions of this research program. Furthermore, understanding the role of ncRNAs in bacterial pathogenesis in lower vertebrates, and the regulation of A. salmonicida endogenous mutagenesis will provide insight into bacterial pathogenesis and evolution. Additionally, mortalities in emerging finfish aquaculture caused by A. salmonicida have raised concern about the efficiency of current vaccine and treatments against furunculosis. The results obtained here will have an impact on vaccine design for finfish, contributing to the Canadian and global aquaculture.