Amsterdam Multidisciplinary Lyme Center (AMLC)

The Amsterdam Multidisciplinary Lyme Center combines clinical care and research on Lyme borreliosis.

Since 2012 the departments of infectious diseases, neurology, dermatology and rheumatology closely collaborate in the clinical care patients with Lyme borreliosis or other tick-borne diseases. We are supported by the departments of pediatrics, medical microbiology and psychiatry.

Since 2005 our research group is part of the Center for Experimental and Molecular Medicine (CEMM). Prof dr T. van der poll is head of the department and Dr J.W.R. Hovius is the AMC principal investigator Ticks & Tick-borne Diseases. Hovius is an internist and infectious diseases specialist and has a PhD in tick-host-pathogen interactions in Lyme borreliosis. Currently, Hovius heads a group consisting of five PhD students; J. Coumou, L. Mason, A. Wagemakers, J. Koetsveld and J.J. Trentelman and one (bio)technician J.I. Ersoz. We closely collaborate with prof dr T.H.B. Geijtenbeek (AMC, CEMM) and prof E. Fikrig (Yale University, Infectious Diseases).

Partners

Our group is financially supported by the AMC, AMC graduate school, and grants from the Netherlands organization for health research and development (ZonMw), including a VENI-grant. Finally, we have received funding from the European Commission within the FP7 program for our collaborative research on anti-tick vaccines - www.ANTIDotE-fp7.org. We perform translational research, bridging basic science and clinical research

Current Research

Our basic research focuses on tick-host-pathogen interactions in Lyme borreliosis. We are interested in how this affects early Lyme borreliosis pathogenesis and how further understanding of the complex interactions can lead to future preventive strategies to combat tick-borne diseases. Our ultimate goal is to identify an anti-tick vaccine to prevent multiple tick-borne diseases. Since 2014 we are the scientific coordinator of an European collaborative project - ANTIDotE – that aims to identify, characterize and develop such a vaccine in collaboration with an international multidisciplinary consortium with partners from Spain, Germany, The Netherlands, The Slovak Republic and The Czech Republic. Furthermore, the AMLC is engaged in several retrospective clinical studies and is about to launch a prospective study in collaboration with other national experts.

Research highlights

Narasimhan# S, Coumou J#, Schuijt TJ, Boder E, Hovius JW*, Fikrig E*. A Tick Gut Protein with Fibronectin III Domains Aids Borrelia burgdorferi Congregation to the Gut during Transmission. PLoS Pathog. 2014 Aug 7;10(8):e1004278.
# and * signify equal contributions.

In this article, in collaboration with Yale University, we describe how Borrelia uses a tick gut protein to egress from the gut to migrate to the tick salivary glands, from where it can be transmitted to the host. We utilized a yeast surface display library of tick gut proteins to perform a global screen for tick gut proteins that might interact with Borrelia membrane proteins. A putative fibronectin type III domain-containing tick gut protein (Ixofin3D) was most frequently identified from this screen and prioritized for further analysis. Immunization against Ixofin3D and RNA interference-mediated reduction in expression of Ixofin3D resulted in decreased spirochete burden in tick salivary glands and in the murine host. Microscopic examination showed decreased aggregation of spirochetes on the gut epithelium concomitant with reduced expression of Ixofin3D. Our observations suggest that the interaction between Borrelia and Ixofin3D facilitates spirochete congregation to the gut during transmission, and provides a "molecular exit" direction for spirochete egress from the gut. Better understanding of the molecular mechanisms underlying the migration of Borrelia within the tick and the subsequent transmission to the host will provide pivotal information that can be used to develop innovative preventive strategies, such as anti-tick vaccines.

Source: Plos Pathogens 2014