TY - JOUR T1 - Proteomic analysis of liver tissue reveals <em>Aeromonas hydrophila</em> infection mediated modulation of host metabolic pathways in <em>Labeo rohita</em> JF - bioRxiv DO - 10.1101/2021.11.16.468918 SP - 2021.11.16.468918 AU - Mehar Un Nissa AU - Nevil Pinto AU - Biplab Ghosh AU - Urvi Singh AU - Mukunda Goswami AU - Sanjeeva Srivastava Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/11/19/2021.11.16.468918.abstract N2 - 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.IMPORTANCE Bacterial 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.AarsAlanine--tRNA ligase OSAtp2b1Calcium-transporting ATPaseAtp6v1aH(+)-transporting two-sector ATPaseAtp6vocV-type proton ATPase proteolipid subunitAtp8ATP synthase protein 8 OSCpt1Carnitine O-palmitoyltransferase OSCyp1aUnspecific monooxygenase OSCyp2f2Cytochrome P450 2F2-like protein OSCyp2g1Cytochrome P450 2G1-like proteinCyp3aCytochrome P450 3A30-like protein OSEprsGlutamyl-tRNA synthetase OSFabpFatty acid-binding brain-like protein OSHsp90aa1Heat shock HSP 90-alpha OSHspa8Heat shock cognate 71 kDa OSMogsMannosyl-oligosaccharide glucosidase-like protein OSNdufa12NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12Ndufa2Complex I-B8 OSNdufa6Complex I-B14Ndufb10Complex I-PDSW OSNdufb6Complex I-B17Ndufs8Complex I-23kDNdufv2NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrialPsma1Proteasome subunit alpha type-1Psma5Proteasome subunit alpha type OSPsma8Proteasome subunit alpha type OSPsmb4Proteasome subunit betaPsmd326S proteasome non-ATPase regulatory subunit 3 OSPsmd626S proteasome non-ATPase regulatory subunit 6 OSQarsGlutamine--tRNA ligase OSRpl1360S ribosomal protein L13 OSRpl7a60S ribosomal protein L7a OSRplp260S acidic ribosomal protein P2 OSRps640S ribosomal protein S6 OSRrbp1Ribosome-binding 1-like isoform X1 OSScp2Acetyl-CoA C-myristoyltransferase OSSec31aTransport Sec31A-like isoform X5 OSTCEPTris(2-carboxyethyl)phosphineTlr4Toll-like receptor 4 ER -