Nissa Mehar Un, Pinto Nevil, Ghosh Biplab, Singh Urvi, Goswami Mukunda, Srivastava Sanjeeva
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Central Institute of Fisheries Education, Indian Council of Agricultural Research, Versova, Mumbai, Maharashtra 400061, India.
J Proteomics. 2023 May 15;279:104870. doi: 10.1016/j.jprot.2023.104870. Epub 2023 Mar 10.
Aeromonas hydrophila (Ah) is a Gram-negative bacterium and a serious global pathogen causing Motile Aeromonas Septicaemia (MAS) in fish leading to global loss in aquaculture. Investigation of the molecular alterations of host tissues such as liver could be a powerful approach to identify mechanistic and diagnostic immune signatures of disease pathogenesis. We performed a proteomic analysis of Labeo rohita liver tissue to examine the protein dynamics in the host cells during Ah infection. The proteomic data was acquired using two strategies; discovery and targeted proteomics. Label-free quantification was performed between Control and challenged group (AH) to identify the differentially expressed proteins (DEPs). A total of 2525 proteins were identified and 157 were DEPs. DEPs include metabolic enzymes (CS, SUCLG2), antioxidative proteins, cytoskeletal proteins and immune related proteins (TLR3, CLEC4E). Pathways like lysosome pathway, apoptosis, metabolism of xenobiotics by cytochrome P450 were enriched by downregulated proteins. However, upregulated proteins majorly mapped to innate immune system, signaling of B cell receptor, proteosome pathway, ribosome, carbon metabolism and protein processing in ER. Our study would help in exploring the role of Toll-like receptors, C-type lectins and, metabolic intermediates like citrate and succinate in Ah pathogenesis to understand the Ah infection in fish. SIGNIFICANCE: Bacterial diseases such as motile aeromonas septicaemia (MAS) are among the most serious problems in aquaculture industry. 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. We examined alterations in the host proteome during MAS caused by Aeromonas hydrophila (Ah) infection, in Labeo rohita liver tissue to find cellular proteins and processes affected by Ah infection. Upregulated proteins belong to innate immune system, signaling of B cell receptor, proteosome pathway, ribosome, carbon metabolism and protein processing. 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.
嗜水气单胞菌(Ah)是一种革兰氏阴性菌,是一种严重的全球病原体,可导致鱼类发生运动性气单胞菌败血症(MAS),给全球水产养殖业造成损失。研究肝脏等宿主组织的分子变化可能是一种强大的方法,可用于识别疾病发病机制的机械性和诊断性免疫特征。我们对印度鲤鱼肝脏组织进行了蛋白质组学分析,以研究Ah感染期间宿主细胞中的蛋白质动态变化。蛋白质组学数据通过两种策略获得:发现型和靶向蛋白质组学。在对照组和感染组(AH)之间进行无标记定量,以鉴定差异表达蛋白(DEP)。共鉴定出2525种蛋白质,其中157种为DEP。DEP包括代谢酶(CS、SUCLG2)、抗氧化蛋白、细胞骨架蛋白和免疫相关蛋白(TLR3、CLEC4E)。下调的蛋白质丰富了溶酶体途径、凋亡、细胞色素P450对外源化合物的代谢等途径。然而,上调的蛋白质主要映射到先天免疫系统、B细胞受体信号传导、蛋白酶体途径、核糖体、碳代谢和内质网中的蛋白质加工。我们的研究将有助于探索Toll样受体、C型凝集素以及柠檬酸盐和琥珀酸盐等代谢中间体在Ah发病机制中的作用,以了解鱼类的Ah感染。意义:运动性气单胞菌败血症(MAS)等细菌性疾病是水产养殖业中最严重的问题之一。靶向宿主代谢的小分子最近已成为传染病潜在的治疗可能性。然而,由于缺乏对发病机制和宿主-病原体相互作用的了解,开发新疗法的能力受到阻碍。我们研究了嗜水气单胞菌(Ah)感染引起印度鲤鱼肝脏组织中MAS期间宿主蛋白质组的变化,以发现受Ah感染影响的细胞蛋白质和过程。上调的蛋白质属于先天免疫系统、B细胞受体信号传导、蛋白酶体途径、核糖体、碳代谢和蛋白质加工。我们的工作通过提供Ah感染期间蛋白质组病理学相关性的更全面图景,朝着利用宿主代谢来靶向疾病迈出了重要一步。