title: Metabolic responses to Orientia tsutsugamushi infection in a mouse model.
abstract: Tsutsugamushi disease is an infectious disease transmitted to humans through the bite of the Orientia tsutsugamushi-infected chigger mite; however, host-pathogen interactions and the precise mechanisms of damage in O. tsutsugamushi infections have not been fully elucidated. Here, we analyzed the global metabolic effects of O. tsutsugamushi infection on the host using 1H-NMR and UPLC-Q-TOF mass spectroscopy coupled with multivariate statistical analysis. In addition, the effect of O. tsutsugamushi infection on metabolite concentrations over time was analyzed by two-way ANOVAs. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed distinct metabolic patterns between control and O. tsutsugamushi-infected mice in liver, spleen, and serum samples. O. tsutsugamushi infection caused decreased energy production and deficiencies in both remethylation sources and glutathione. In addition, O. tsutsugamushi infection accelerated uncommon energy production pathways (i.e., excess fatty acid and protein oxidation) in host body. Infection resulted in an enlarged spleen with distinct phospholipid and amino acid characteristics. This study suggests that metabolite profiling of multiple organ tissues and serum could provide insight into global metabolic changes and mechanisms of pathology in O. tsutsugamushi-infected hosts.
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea; KM Health Technology Research Group of Medical Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
authors.forename: Jeeyoun
authors.initials: J
authors.lastname: Jung
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea.
authors.forename: Youngae
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Division of Zoonoses, Center for Immunology and Pathology, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Byoungchul
authors.initials: B
authors.lastname: Gill
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea.
authors.forename: Changhun
authors.initials: C
authors.lastname: Kim
authors.affiliation: Division of Zoonoses, Center for Immunology and Pathology, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Kyu-Jam
authors.initials: KJ
authors.lastname: Hwang
authors.affiliation: Division of Zoonoses, Center for Immunology and Pathology, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Ju
authors.affiliation: Division of Metabolic Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Hye-Ja
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Zoonoses, Center for Immunology and Pathology, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea; Division of Influenza Virus, Center for Infectious Disease, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Chu
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Geum-Sook
authors.initials: GS
authors.lastname: Hwang
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005347:Fibroblasts; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012285:Orientia tsutsugamushi / Q000502:physiology*; D012612:Scrub Typhus / Q000378:metabolism* / Q000473:pathology; D013154:Spleen