Genetic background amplifies the effect of immunodeficiency in antibiotic efficacy against Borrelia burgdorferi Unrecognized immunodeficiency has been proposed as a possible cause of failure of antibiotics to resolve symptoms of Lyme disease. Here, we examined the efficacy of doxycycline in different immune deficient mice to identify defects that impair antibiotic treatment outcomes. We found that doxycycline had significantly lower efficacy in the absence of adaptive immunity, specifically B cells. This effect was most pronounced in immunodeficientC3H mice compared with C57BL/6 mice...

Retrotransposon-based bloodmeal analysis of nymphal deer ticks demonstrates spatiotemporal diversity of Borrelia burgdorferi and Babesia microti reservoirs The white-footed mouse is considered to be the primary host for subadult deer ticks and the most important reservoir host for these and other disease agents. Local transmission is thought to be modulated by less reservoir competent hosts such as deer diverting ticks from feeding on mice. We measured the proportion of mouse fed or deer fed host-seeking nymphs from 4 sites during 2 transmission seasons by bloodmeal remnant analysis using a...

Innate Immune Memory to Repeated Borrelia burgdorferi Exposure Correlates with Murine In Vivo Inflammatory Phenotypes Factors that determine the presence of skin inflammation and the joint arthritis susceptibility in the host are only partially characterized. We show in this study that murine fibroblast-like synoviocytes display trained immunity, a program in some cells that results in increased inflammatory responses if the cell has previously come in contact with a stimulus, and that trained immunity in fibroblast-like synoviocytes tested ex vivo correlates with Lyme arthritis...

Protective Immunity and New Vaccines for Lyme Disease Discovery of the mechanism of action of the first vaccine catalyzed the development of new strategies to control Lyme disease that bypassed direct vaccination of the human host. Thus, novel prevention concepts center on proteins produced by B. burgdorferi during tick transit and on tick proteins that mediate feeding and pathogen transmission. A burgeoning area of research is tick immunity as it can unlock mechanistic pathways that could be targeted for disruption.  

Blood Smears Have Poor Sensitivity for Confirming Borrelia miyamotoi Disease Borrelia miyamotoi disease (BMD) is a newly recognized borreliosis that is cotransmitted by ticks wherever Lyme disease is zoonotic. To determine whether blood smears may detect B. miyamotoi in the blood of acute BMD patients, we made standard malariological thick smears from anticoagulated blood samples that were previously determined to contain this agent (by PCR) and analyzed them for morphological evidence of spirochetes. We found that in strong contrast to the diagnosis of typical relapsing fever, microscopy of...

Early Questing by Lone Star Tick Larvae, New York and Massachusetts, USA, 2018 Subtropical lone star tick larvae typically emerge in late summer. We found clusters of host-seeking lone star tick larvae during early June 2018 in New York and Massachusetts, USA. Invasion and persistence of this tick in more northern locations may have been promoted by adaptation to an accelerated life cycle.  

Strain-specific joint invasion and colonization by Lyme disease spirochetes is promoted by outer surface protein C The basis for tissue tropism is poorly understood, but has been long hypothesized to involve strain-specific interactions with host components in the target tissue. OspC (outer surface protein C) is a highly variable outer surface protein required for infectivity, and sequence differences in OspC are associated with variation in tissue invasiveness, but whether OspC directly influences tropism is unknown. We found that OspC binds to the extracellular matrix (ECM) components...

The intergenic small non-coding RNA ittA is required for optimal infectivity and tissue tropism in Borrelia burgdorferi Post-transcriptional regulation via small regulatory RNAs (sRNAs) has been implicated in diverse regulatory processes in bacteria, including virulence. One class of sRNAs, termed trans-acting sRNAs, can affect the stability and/or the translational efficiency of regulated transcripts. In this study, we utilized a collaborative approach that employed data from infection with the Borrelia burgdorferi Tn library, coupled with Tn-seq, together with borrelial sRNA and total RNA...

Design of a broadly reactive Lyme disease vaccine We designed a six component vaccine that elicits antibody (Ab) responses against all Borrelia strains that commonly cause Lyme disease in humans. The outer surface protein A (OspA) of Borrelia was fused to a bacterial ferritin to generate self-assembling nanoparticles. OspA-ferritin nanoparticles elicited durable high titer Ab responses to the seven major serotypes in mice and non-human primates at titers higher than a previously licensed vaccine. This response was durable in rhesus macaques for more than 6 months. Vaccination with adjuvanted...

Host Metabolic Response in Early Lyme Disease Metabolic biosignatures of patients with early Lyme disease can potentially provide diagnostic targets as well as highlight metabolic pathways that contribute to pathogenesis. Metabolic pathway analysis and chemical identification of metabolites with LC-tandem mass spectrometry (LC-MS/MS) demonstrated alterations of eicosanoid, bile acid, sphingolipid, glycerophospholipid, and acylcarnitine metabolic pathways during early Lyme disease. The findings demonstrated that infection of humans with B. burgdorferi alters defined metabolic pathways that...