title: Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut.
abstract: The causative agent of Lyme borreliosis, Borrelia burgdorferi, is transmitted by Ixodes ticks. During tick feeding, B. burgdorferi migrates from the tick gut to the salivary glands from where transmission to the host occurs. B. burgdorferi-interacting tick proteins might serve as vaccine targets to thwart B. burgdorferi transmission. A previous screening for B. burgdorferi-interacting Ixodes scapularis gut proteins identified an I. scapularis putative dystroglycan protein (ISCW015049). Here, we describe the ISCW015049's protein structure and its cellular location in the tick gut in relation to B. burgdorferi migration. Secondly, in vivo B. burgdorferi-tick attachment murine models were performed to study the role of ISCW015049 during B. burgdorferi migration and transmission. In silico analysis confirmed that ISCW015049 is similar to dystroglycan and was named I. scapularis dystroglycan-like protein (ISDLP). Confocal microscopy of gut tissue showed that ISDLP is expressed on the surface of gut cells, is upregulated during tick feeding, and is expressed significantly higher in infected ticks compared to uninfected ticks. Inhibition of ISDLP by RNA interference (RNAi) resulted in lower B. burgdorferi transmission to mice. In conclusion, we have identified a dystroglycan-like protein in I. scapularis gut that can bind to B. burgdorferi and promotes B. burgdorferi migration from the tick gut. Key messages: B. burgdorferi exploits tick proteins to orchestrate its transmission to the host. B. burgdorferi is able bind to an I. scapularis dystroglycan-like protein (ISDLP). Inhibition of ISDLP in ticks results in lower B. burgdorferi transmission to mice. ISDLP is a potential target to prevent Lyme borreliosis.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands. j.coumou@amc.nl.
authors.forename: Jeroen
authors.identifier: http://orcid.org/0000-0002-4792-2710
authors.initials: J
authors.lastname: Coumou
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, 06511, New Haven, CT, USA.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Narasimhan
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Jos J
authors.initials: JJ
authors.lastname: Trentelman
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Alex
authors.initials: A
authors.lastname: Wagemakers
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: Koetsveld
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Jasmin I
authors.initials: JI
authors.lastname: Ersoz
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Oei
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, 06511, New Haven, CT, USA.
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Joppe W
authors.initials: JW
authors.lastname: Hovius
mesh_terms: D000818:Animals; D060829:Arthropod Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D025065:Borrelia burgdorferi / Q000502:physiology*; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007114:Immunization; D018884:Ixodes / Q000235:genetics / Q000382:microbiology* / Q000502:physiology; D008193:Lyme Disease / Q000378:metabolism / Q000517:prevention & control* / Q000635:transmission*; D022123:Lyme Disease Vaccines / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D000067492:RNAi Therapeutics; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D060829:Arthropod Proteins; D022123:Lyme Disease Vaccines; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D049030:Dystroglycans
keywords: Borrelia burgdorferi; Ixodes scapularis; Lyme borreliosis; Pathogen transmission; Tick-borne diseases; Vaccination