Host Metabolic Response in Early Lyme Disease

Abstract

Lyme disease is a tick-borne bacterial illness that occurs in areas of North America, Europe, and Asia. Early infection typically presents as generalized symptoms with an erythema migrans (EM) skin lesion. Dissemination of the pathogen Borrelia burgdorferi can result in multiple EM skin lesions or in extracutaneous manifestations such as Lyme neuroborreliosis. Metabolic biosignatures of patients with early Lyme disease can potentially provide diagnostic targets, as well as highlight metabolic pathways that contribute to pathogenesis. Sera from well-characterized patients diagnosed with either early localized Lyme disease (ELL) or early disseminated Lyme disease (EDL), plus healthy individuals (HC), from the United States were analyzed by liquid chromatography-mass spectrometry (LC-MS). Comparative analyses were performed between ELL, or EDL, or ELL combined with EDL, and the HC to develop biosignatures present in early Lyme disease. A direct comparison between ELL and EDL was also performed to develop a biosignature for stages of early Lyme disease. Metabolic pathway analysis and chemical identification of metabolites with LC-tandem mass spectrometry (LC-MS/MS) demonstrated

Lipid hijacking: A unifying theme in vector-borne diseases

“…Despite their extracellular lifecycle, there is evidence that B. burgdorferi infection influences lipid metabolism in the host. A recent study in Lyme disease patients demonstrated that B. burgdorferi infection increases serum levels of lysophosphatidylcholine (LPC), a variant of PC that contains one fatty acyl chain ( Fitzgerald et al, 2020 ). Lysophospholipids are generated as a byproduct of phospholipid degradation or an intermediate of phospholipid synthesis.…”

“…Additionally, severe outcomes during Lyme disease may be associated with host metabolism. Patients with early disseminated Lyme disease have more pronounced metabolic signatures than those with early localized Lyme disease ( Fitzgerald et al, 2020 ). One such metabolic signature is the differential production of eicosanoids that correlate with symptoms such as Lyme arthritis ( Blaho et al, 2009 ; Fitzgerald et al, 2020 ).…”

“…However, most microbes considered ‘human pathogens’ are not detrimental to the arthropod, which is a phenomenon that is not well understood. For example, lipid utilization by microbes does not appear to impair arthropod fitness, yet lipid dysregulation is often a symptom of severe disease in mammals ( Ghosh et al, 2012 ; Biswas et al, 2015 ; Toledo et al, 2015a ; Costa et al, 2018 ; Werling et al, 2019 ; Cordy et al, 2019 ; Fitzgerald et al, 2020 ). This observation is intriguing, considering the general lipid compositions of invertebrate vectors and mammalian hosts are fairly similar.…”

Development of a capture sequencing assay for enhanced detection and genotyping of tick-borne pathogens

“…Serology has been shown to be more useful in Lyme disease diagnosis, but currently employed serologic assays can also suffer from intrinsic limitations, including inadequate sensitivity and specificity for samples collected early in disease as well as subjectivity in data interpretation 11 , 40 – 42 . As a result, alternative platforms for diagnosis of acute Lyme disease have been pursued, including metabolomics, transcriptomics and modifications of PCR such as digital droplet PCR 43 – 45 . In specimens with active bacteremia, TBDCapSeq can address the sensitivity limitations of other molecular assays and provide a new approach for genomic and pathogenesis studies of B. burgdorferi s.s .…”

Discovery and Surveillance of Tick-Borne Pathogens

“…This allows simultaneous serologic detection and discrimination of antibodies to multiple TBD in a single assay ( Tokarz et al 2018a ). Metabolomic analyses have identified metabolic signatures unique to early Lyme borreliosis ( Molins et al 2015 , Fitzgerald et al 2020 ). These studies have been extended to Southern Tick Associated Rash Illness, an illness of unknown etiology ( Molins et al 2017 ).…”