Hard-bodied Ixodes ticks are the main vector for Borrelia burgdorferi, the causative agent of Lyme borreliosis. These same Ixodes tick species are known to carry other microorganisms, such as Rickettsia helvetica and Borrelia miyamotoi. Little was known about these potential human pathogens that were found in Ixodes ticks across the northern hemisphere.In this thesis, the presence of other tick-borne pathogens in patients suspected of Lyme borreliosis and in patients with fever after a tick-bite was studied, both by molecular and serological methods. Also, a novel method for cultivation of B. miyamotoi from human blood was described and used to obtain the first clinical isolates from patients with Borrelia miyamotoi disease. Subsequently, these clinical isolates, as well as B. miyamotoi lab strains, were used to study the antimicrobial susceptibility of B. miyamotoi, compared to other relapsing fever Borrelia and B. burgdorferi isolates.It was previously shown that B. miyamotoi is able to evade antibody-mediated killing by expression of variable major proteins (Vmps) both in vitro and in vivo. As part of this thesis, Vmps were studied as novel seromarkers for diagnosis of patients with PCR-proven Borrelia miyamotoi disease. In addition, identified Vmps were used to diagnose the first immunocompetent patient with Borrelia miyamotoi disease in Western Europe. Lastly, this thesis uncovered that a large degree of homology between Vmps and a peptide commonly used for serodiagnosis of Lyme disease, leads to false positive results in a widely used test for diagnosis of Lyme disease
