No abstract

Lyme borreliosis (LB), caused by bacteria of the Borrelia burgdorferi sensu lato ( Borrelia) species, is the most common tick-borne infection in the northern hemisphere. LB diagnostics is based on clinical evaluation of the patient and on laboratory testing, where the main method is the detection of Borrelia specific antibodies in patient samples. There are, however, shortcomings in the current serology based LB diagnostics, especially its inability to differentiate ongoing infection from a previously treated one. Identification of specific biomarkers of diseases is a growing application of metabolomics. One of the main methods of metabolomics is nuclear magnetic resonance (NMR) spectroscopy. In the present study, our aim was to analyze whether Borrelia growth in vitro and infection in vivo in mice causes specific metabolite differences, and whether NMR can be used to detect them. For this purpose, we performed NMR analyses of in vitro culture medium samples, and of serum and urine samples of Borrelia infected and control mice. The results show, that there were significant differences in the concentrations of several amino acids, energy metabolites and aromatic compounds between Borrelia culture and control media, and between infected and control mouse serum and urine samples. For example, the concentration of L -phenylalanine increases in the Borrelia growth medium and in serum of infected mice, whereas the concentrations of allantoin and trigonelline decrease in the urine of infected mice. Therefore, we conclude that Borrelia infection causes measurable metabolome differences in vitro and in Borrelia infected mouse serum and urine samples, and that these can be detected with NMR.

No abstract

Lyme borreliosis is a tick‐borne disease caused by Borrelia burgdorferi sensu lato spirochetes (Lyme borreliae). When the disease affects the central nervous system, it is referred to as neuroborreliosis. In Europe, neuroborreliosis is most often caused by Borrelia garinii. Although it is known that in the host Lyme borreliae spread from the tick bite site to distant tissues via the blood vasculature, the adherence of Lyme borreliae to human brain microvascular endothelial cells has not been studied before. Decorin binding proteins are adhesins expressed on Lyme borreliae. They mediate the adhesion of Lyme borreliae to decorin and biglycan, and the lysine residues located in the binding site of decorin binding proteins are important to the binding activity. In this study, we show that lysine residues located in the canonical binding site can also be found in decorin binding proteins of Borrelia garinii, and that these lysines contribute to biglycan and decorin binding. Most importantly, we show that the lysine residues are crucial for the binding of Lyme borreliae to decorin and biglycan expressing human brain microvascular endothelial cells, which in turn suggests that they are involved in the pathogenesis of neuroborreliosis.