Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 94; no. 3; pp. 361 - 370
• Main Authors: Coumou, Jeroen, Narasimhan, Sukanya, Trentelman, Jos J., Wagemakers, Alex, Koetsveld, Joris, Ersoz, Jasmin I., Oei, Anneke, Fikrig, Erol, Hovius, Joppe W.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2016; Springer Nature B.V
• Subjects: Animals; Arthropod Proteins - genetics; Arthropod Proteins - metabolism; Arthropod Proteins - therapeutic use; Biomedical and Life Sciences; Biomedicine; Borrelia burgdorferi; Borrelia burgdorferi - physiology; Dystroglycans - genetics; Dystroglycans - metabolism; Dystroglycans - therapeutic use; Human Genetics; Humans; Immunization; Internal Medicine; Ixodes; Ixodes - genetics; Ixodes - microbiology; Ixodes - physiology; Ixodes scapularis; Ixodidae; Lyme Disease - metabolism; Lyme Disease - prevention & control; Lyme Disease - transmission; Lyme Disease Vaccines - genetics; Lyme Disease Vaccines - metabolism; Lyme Disease Vaccines - therapeutic use; Mice; Molecular Medicine; Original; Original Article; Rabbits; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - therapeutic use; RNA, Small Interfering - genetics; RNA, Small Interfering - therapeutic use; RNAi Therapeutics; Lyme borreliosis; Pathogen transmission; Vaccination; Tick-borne diseases; Borrelia burgdorferi; Ixodes scapularis
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-015-1365-0

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.