Luce-Fedrow A, Lehman ML, Kelly DJ, Mullins K, Maina AN, Stewart RL, Ge H, John HS, Jiang J, Richards AL , 2018. A review of scrub typhus (Orientia tsutsugamushi and related organisms): then, now, and tomorrow. Trop Med Infect Dis 3: 8.
Diaz FE, Abarca K, Kalergis AM , 2018. An update on host-pathogen interplay and modulation of immune responses during Orientia tsutsugamushi infection. Clin Microbiol Rev 31: e000076-17.
Xu G, Walker DH, Jupiter D, Melby PC, Arcari CM , 2017. A review of the global epidemiology of scrub typhus. PLoS Negl Trop Dis 11: e0006062.
Rose W, Kang G, Verghese VP, Candassamy S, Samuel P, Prakash JJA, Muliyil J , 2019. Risk factors for acquisition of scrub typhus in children admitted to a tertiary centre and its surrounding districts in South India: a case control study. BMC Infect Dis 19: 665.
Elliott I, Pearson I, Dahal P, Thomas NV, Roberts T, Newton PN , 2019. Scrub typhus ecology: a systematic review of Orientia in vectors and hosts. Parasit Vectors 12: 513.
Kim S, Kim JS, Lee H , 2010. Epidemiological characteristics of scrub typhus in Korea, 2009. Osong Public Health Res Perspect 1: 55–60.
Noh M, Lee Y, Chu C, Gwack J, Youn SK, Huh S , 2013. Are there spatial and temporal correlations in the incidence distribution of scrub typhus in Korea? Osong Public Health Res Perspect 4: 39–44.
Manosroi J, Chutipongvivate S, Auwanit W, Manosroi A , 2003. Early diagnosis of scrub typhus in Thailand from clinical specimens by nested polymerase chain reaction. Southeast Asian J Trop Med Public Health 34: 831–838.
Rodkvamtook W et al.2015. Dot-ELISA rapid test using recombinant 56-kDa protein antigens for serodiagnosis of scrub typhus. Am J Trop Med Hyg 92: 967–971.
Pote K, Narang R, Deshmukh P , 2018. Diagnostic performance of serological tests to detect antibodies against acute scrub typhus infection in central India. Indian J Med Microbiol 36: 108–112.
Couturier MR, Graf EH, Griffin AT , 2014. Urine antigen tests for the diagnosis of respiratory infections: legionellosis, histoplasmosis, pneumococcal pneumonia. Clin Lab Med 34: 219–236.
Nagana Gowda GA, Raftery D , 2013. Biomarker discovery and translation in metabolomics. Curr Metabolomics 1: 227–240.
Jung J, Jung Y, Gill B, Kim C, Hwang KJ, Ju YR, Lee HJ, Chu H, Hwang GS , 2015. Metabolic responses to Orientia tsutsugamushi infection in a mouse model. PLoS Negl Trop Dis 9: e3427.
Kim IS, Seong SY, Woo SG, Choi MS, Chang WH , 1993. High-level expression of a 56-kilodalton protein gene (bor56) of Rickettsia tsutsugamushi Boryong and its application to enzyme-linked immunosorbent assays. J Clin Microbiol 31: 598–605.
Chang WH, Kang JS, Lee WK, Choi MS, Lee JH , 1990. Serological classification by monoclonal antibodies of Rickettsia tsutsugamushi isolated in Korea. J Clin Microbiol 28: 685–688.
Tamura A, Urakami H , 1981. Easy method for infectivity titration of Rickettsia tsutsugamushi by infected cell counting. Nihon Saikingaku Zasshi 36: 783–785.
Metsalu T, Vilo J , 2015. ClustVis: a web tool for visualizing clustering of multivariate data using principal component analysis and heatmap. Nucl Acids Res 43: W566–W570.
Kramer A, Green J, Pollard J Jr , Tugendreich S , 2014. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30: 523–530.
Everts B et al.2014. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKvarepsilon supports the anabolic demands of dendritic cell activation. Nat Immunol 15: 323–332.
Isa F et al.2018. Mass spectrometric identification of urinary biomarkers of pulmonary tuberculosis. EBioMedicine 31: 157–165.
Foschi C, Laghi L, D’Antuono A, Gaspari V, Zhu C, Dellarosa N, Salvo M, Marangoni A , 2018. Urine metabolome in women with Chlamydia trachomatis infection. PLoS One 13: e0194827.
Al-Mubarak R, Vander Heiden J, Broeckling CD, Balagon M, Brennan PJ, Vissa VD , 2011. Serum metabolomics reveals higher levels of polyunsaturated fatty acids in lepromatous leprosy: potential markers for susceptibility and pathogenesis. PLoS Negl Trop Dis 5: e1303.
Zhang A, Sun H, Wang P, Han Y, Wang X , 2012. Recent and potential developments of biofluid analyses in metabolomics. J Proteomics 75: 1079–1088.
Mathis D, Shoelson SE , 2011. Immunometabolism: an emerging frontier. Nat Rev Immunol 11: 81.
Chao CC, Ingram BO, Lurchachaiwong W, Ching WM , 2018. Metabolic characterization of serum from mice challenged with Orientia tsutsugamushi-infected mites. New Microbes New Infect 23: 70–76.
Prachason T, Konhan K, Pongnarin P, Chatsiricharoenkul S, Suputtamongkol Y, Limwongse C , 2012. Activation of indoleamine 2,3-dioxygenase in patients with scrub typhus and its role in growth restriction of Orientia tsutsugamushi. PLoS Negl Trop Dis 6: e1731.
Minois N , 2014. Molecular basis of the ‘anti-aging’ effect of spermidine and other natural polyamines: a mini-review. Gerontology 60: 319–326.
Ko Y, Choi JH, Ha NY, Kim IS, Cho NH, Choi MS , 2013. Active escape of Orientia tsutsugamushi from cellular autophagy. Infect Immun 81: 552–559.
Kim DM, Kang DW, Kim JO, Chung JH, Kim HL, Park CY, Lim SC , 2008. Acute renal failure due to acute tubular necrosis caused by direct invasion of Orientia tsutsugamushi. J Clin Microbiol 46: 1548–1550.
Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S , 1991. Molecular cloning and characterization of the rat NMDA receptor. Nature 354: 31–37.
Hardingham GE, Bading H , 2003. The yin and yang of NMDA receptor signalling. Trends Neurosci 26: 81–89.
Choi DW, Koh JY, Peters S , 1988. Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J Neurosci 8: 185–196.
Parsons MP, Raymond LA , 2014. Extrasynaptic NMDA receptor involvement in central nervous system disorders. Neuron 82: 279–293.
Leung JC, Marphis T, Craver RD, Silverstein DM , 2004. Altered NMDA receptor expression in renal toxicity: protection with a receptor antagonist. Kidney Int 66: 167–176.
Qu Q, Zeng F, Liu X, Wang QJ, Deng F , 2016. Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer. Cell Death Dis 7: e2226.
Tarasenko TN, Cusmano-Ozog K, McGuire PJ , 2018. Tissue acylcarnitine status in a mouse model of mitochondrial beta-oxidation deficiency during metabolic decompensation due to influenza virus infection. Mol Genet Metab 125: 144–152.
Renesto P, Ogata H, Audic S, Claverie JM, Raoult D , 2005. Some lessons from Rickettsia genomics. FEMS Microbiol Rev 29: 99–117.
Ogawa M, Fukasawa M, Satoh M, Hanada K, Saijo M, Uchiyama T, Ando S , 2014. The intracellular pathogen Orientia tsutsugamushi responsible for scrub typhus induces lipid droplet formation in mouse fibroblasts. Microbes Infect 16: 962–966.
Tipthara P, Thongboonkerd V , 2016. Differential human urinary lipid profiles using various lipid-extraction protocols: MALDI-TOF and LIFT-TOF/TOF analyses. Sci Rep 6: 33756.
|Past two years||Past Year||Past 30 Days|
|Full Text Views||90||90||9|
Scrub typhus is an acute febrile, mite-borne disease endemic to the Asia–Pacific region. In South Korea, it is a seasonal disease that occurs frequently in the autumn, and its incidence has increased steadily. In this study, we used a liquid chromatography and flow injection analysis–tandem mass spectrometry-based targeted urine metabolomics approach to evaluate the host response to Orientia tsutsugamushi infection. Balb/c mice were infected with O. tsutsugamushi Boryong, and their urine metabolite profile was examined. Metabolites that differed significantly between the experimental groups were identified using the Kruskal–Wallis test. Sixty-five differential metabolites were identified. The principal metabolite classes were acylcarnitines, glycerophospholipids, biogenic amines, and amino acids. An ingenuity pathway analysis revealed that several toxic (cardiotoxic, hepatotoxic, and nephrotoxic) metabolites are induced by scrub typhus infection. This is the first report of urinary metabolite biomarkers of scrub typhus infection and it enhances our understanding of the metabolic pathways involved.
These authors contributed equally to this work.
Financial support: This work was supported by intramural grants from KNIH (2018-NI002-02).
Authors’ addresses: Sangho Choi, Hee-Bin Park, Sung Soon Kim, and Hyuk Chu, Division of Zoonotic and Vector Borne Disease Research, Center for Infectious Disease Research, National Institute of Infectious Disease, National Institute of Health, Korea Disease Control and Prevention Agency, Osong-eup, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea, E-mails: firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, and email@example.com. Do-Hwan Ahn and Seong Beom Cho, Division of Healthcare and Artificial Intelligence, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-eup, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea, E-mails: firstname.lastname@example.org and email@example.com. Min-Gyu Yoo and Hye-Ja Lee, Division of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-eup, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea, E-mails: firstname.lastname@example.org and email@example.com.