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.
Highlights
IntroductionA mite-borne disease, is the causative agent of scrub typhus (tsutsugamushi disease), the most prevalent febrile illness in the Asia-Pacific region [1,2]
Orientia tsutsugamushi, a mite-borne disease, is the causative agent of scrub typhus, the most prevalent febrile illness in the Asia-Pacific region [1,2]
The extent of pathological change in host organs has been well documented by several studies, but the precise mechanism of damage caused by O. tsutsugamushi infection remains unclear
Summary
A mite-borne disease, is the causative agent of scrub typhus (tsutsugamushi disease), the most prevalent febrile illness in the Asia-Pacific region [1,2]. This disease is characterized by fever, exanthematous rash, eschar, pneumonitis, meningitis, myalgia, and diffuse lymphadenopathy, symptoms similar to those of other acute febrile illnesses such as murine typhus, dengue fever, and viral hemorrhagic fevers. The extent of pathological change in host organs has been well documented by several studies, but the precise mechanism of damage caused by O. tsutsugamushi infection remains unclear. Novel approaches are required to explore the pathogenesis of O. tsutsugamushi
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