Proteomic analysis of liver tissue reveals Aeromonas hydrophila infection mediated modulation of host metabolic pathways in Labeo rohita

Abstract

Aeromonas hydrophila (Ah) is an opportunistic Gram-negative bacterium and a serious global pathogen causing Motile Aeromonas Septicaemia (MAS) in fish and many other vertebrates. The pathogenesis of aeromonas septicaemia is complex and involves multiple perturbed pathways. Molecular analysis of host tissues could be a powerful approach to identify mechanistic and diagnostic immune signatures of disease. We performed a deep proteomic analysis of Labeo rohita liver tissue to examine changes in the host proteome during Ah infection. A total of 2525 proteins were identified of which 158 were found differentially expressed during Ah infection. Functional analysis of significant proteins identified the dysregulation of several metabolic enzymes, antioxidative proteins, cytoskeletal proteins and immune related proteins. Proteomic analysis revealed the alterations in the cellular defence mechanisms including phagolysosomal killing and apoptosis during Ah infection. Our systemic approach revealed the protein dynamics in the host cells to explore the putative biological processes underlying the metabolic reprogramming of the host cells during Ah infection. Our findings paved the way for future research into the role of Toll-like receptors (Tlr3), C-type lectins (Clec4e) and metabolic enzymes in Ah pathogenesis leading towards host directed immunotherapies to tackle the Ah infection in fish. IMPORTANCEBacterial disease is one of the most serious problems in aquaculture industry. Aeromonas hydrophila (Ah), a Gram-negative bacterium causes motile aeromonas septicaemia (MAS) in fish. Small molecules that target the metabolism of the host have recently emerged as potential treatment possibilities in infectious diseases. However, the ability to develop new therapies is hampered due to lack of knowledge about pathogenesis mechanisms and host-pathogen interactions. Molecular level analysis of host tissues could be helpful in finding mechanistic immunological markers of diseases. We examined alterations in the host proteome during Ah infection in Labeo rohita liver tissue to find cellular proteins and processes affected by Ah infection. Our systemic approach revealed protein dynamics underlying the host cells metabolic reprogramming during Ah infection. Our work is an important step towards leveraging host metabolism in targeting the disease by providing a bigger picture on proteome pathology correlation during Ah infection.