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Proteomic analysis in Caenorhabditis elegans challenges with Klebsiella pneumoniae revealed the regulation of TOR pathway against infection Arumugam Kamaladevi1, Kundu Suman2 and Krishnaswamy Balamurugan1* 1 Department of Biotechnology, Alagappa University, Science Campus, Karaikudi- 630003 2 Department of Biochemistry, University of Delhi South Campus, New Delhi-110021 *Corresponding author E-mail: [email protected] Host-pathogen interaction studies at the protein level attract greater interest by providing profound knowledge on different dimensions of interface between host and pathogen. The alarming increase of epidemic infections by several drug-resistant bacteria renowned the necessity of insightful knowledge on microbial pathogenicity and host immune defense at protein level. The recent advent in proteomic tools advances our perspectives on hostpathogen interaction by deciphering the possible molecular mechanism(s) at both ends. Klebsiella pneumoniae is a potent Gram-negative bacterium belongs to the family of Enterobacteriaceae causes several acute to chronic dreadful infections in human. Hitherto, the lack of understanding on host defense mechanism and scanty availability of suitable model organisms make the researchers unsuccessful to come out with appropriate therapy. Caenorhabditis elegans is a well established model system to study the host-pathogen interactions at both transcriptional and translational level against different bacterial infections. Earlier, our lab has analyzed the changes in host proteome against diverse Gramnegative bacterial pathogens such as Salmonella Typhi, Vibrio alginolyticus, Proteus mirabilis, Pseudomonas aeruginosa and Shigella Spp. The results suggested that C. elegans exhibited a specific innate immune response against different pathogens by regulating the proteins like PDI-2, DAF-21 and EEF-2 against V. alginolyticus, P. mirabilis and P. aeruginosa respectively. Since the experimental out-comes from C. elegans were highly comparable to higher animals/mammals, the present study was carried out to understand the alterations in host proteome against K. pneumoniae infection. Comparison of protein profiling by MALDI-MS/MS and LC-MS/MS of nematodes challenged with K. pneumoniae identified many (~200) host encoded regulatory proteins. Functional bioinformatics analyses of identified proteins suggested that the metabolic and dauer formation pathways were over-represented. The increased level of intestinal atrophy and ROS generation indicated that the regulation of metabolic pathway was mediated through TOR. The downregulation of upstream regulators TOR pathway in immunoblotting analysis confirmed the involvement of this pathway against K. pneumoniae infection. Furthermore, the susceptibility of TOR pathway specific C. elegans mutants towards K. pneumoniae validated the involvement of TOR pathway in host defense against K. pneumoniae. Keywords: Caenorhabditis elegans, Klebsiella pneumoniae, host-pathogen interaction.