DiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporamaDiaporama
Home
Home   >   PhD topics   >   2015

2015

Back to search form

How the vector and host skin microbiota influence Lyme disease ?

Research unit

EA 7290 - Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë
Institut de bactériologie 3 rue Koeberlé 67000 Strasbourg

Group

Name: Groupe Borreliose de Lyme

Group leader: BOULANGER Nathalie - nboulanger@unistra.fr

Group leader's phone: 0368853796

Website: Visit website

Group organization:
- Chercheurs: 4
- ITA: 2
- Doctorants: 3
- Post-Docs: 0
- Autres: 0

Publications of the team linked to the topic (3 last years):
1) Smuggling across the Border: How Arthropod-Borne Pathogens Evade and Exploit the Host Defense System of the Skin
Q. BERNARD, B. JAULHAC, N. BOULANGER.
J Invest Dermatol, 2013,Dec 28. doi: 10.1038/jid.2014.36

2) Lyme Neuroborreliosis and Dementia
F. BLANC, N. PHILIPPI, B. CRETIN, C. KLEITZ, L. BERLY, B. JUNG, S. KREMER, I.J. NAMER, F. SELLAL, B. JAULHAC, J. DE SEZE
J. Alzheimers Dis. 2014, Apr.24

3) Proteomic analysis of three Borrelia burgdorferi sensu lato native species and disseminating clones : Relevance for Lyme vaccine design
G. SCHNELL, A. BOEUF, B. JAULHAC, N. BOULANGER, E. COLLIN, C. BARTHEL,
S. DE MARTINO, L. EHRET-SABATIER
Proteomics, 2014 – Dec. 5

About PhD

PhD Director: JAULHAC Benoît - jaulhac@unistra.fr

Phone: 0369551452

Junior advisor: non

Co-tutely: oui

Co-Director: FIKRIG Erol
University of Co-Director: Yale University School of Medicine New Haven

About PhD topic :

Title: How the vector and host skin microbiota influence Lyme disease ?

Project: Goal: This project will address if tick and host skin microbiota influence the ability of Borrelia (B.) burgdorferi to be transmitted from ticks to mice (the host).
Significance
       Lyme disease is the most common tick-borne illness in North America and Western Europe. The causative agent, B. burgdorferi, is transmitted from Ixodes ticks to the mammalian host, and can cause various diseases. Ixodes ricinus ticks are the primary vector in Western Europe and I. scapularis ticks the principle vector in North America. These ticks are closely related, but not identical. Understanding the factors that contribute to transmission may lead to new strategies to prevent infection.

In the last few years, it has become evident that interactions between commensal bacteria and the vertebrate gut direct host immunity and modulate disease outcomes in multiple infectious, metabolic and inflammatory diseases. Recent studies demonstrate that diverse bacteria inhabit the arthropod gut, and might be essential players in shaping the vector's stand-off with infectious agents. Our recent work, demonstrated that microbiota of the I. scapularis modulate the integrity of the gut barrier and impact B. burgdorferi colonization and suggest that tick gut microbiota might also play a critical role in Borrelia transmission to the host.
In this proposal we will validate these initial findings and provide a detailed mechanistic understanding of the vector/host microbiota-Borrelia interactions in the context of transmission to the host.

Approach
We will explore how the vector (tick gut) and the host skin (mouse) microbiota alters B. burgdorferi transmission from tick to mice and: (1) characterize the vector and host skin microbiota (2) determine if these microbiota alters B. burgdorferi transmission to the host, (3) elucidate the molecular pathways involved in this process. These studies will enhance our understanding of the processes that contribute to Borrelia transmission to mice, lead to new strategies to interrupt the life cycle of Borrelia, and increase our molecular understanding of the role of the arthropod and the host microbiota in the transmission of pathogens.

Aim 1. Characterize the microbiota composition of the vector (both I. scapularis and I. ricinus nymphs) and the mouse skin. We will extract DNA from the tick gut and the mouse skin and then proceed to 16S NGS analysis. A comparative analysis of these microbiota will be done.

Aim 2. Determine whether vector and host microbiota influence Borrelia transmission by I. scapularis/ricinus to mice. The gut microbiota of nymphal ticks infected with Borrelia will be perturbed by antibiotic treatment of ticks infected with gentamicin-resistant Borrelia or by raising the nymphal ticks in sterile chambers. The efficiency of tick engorgement, B. burgdorferi growth and migration in ticks, and transmission to mice will be assessed. In order to investigate if the mouse skin microbiota influence the transmission Borrelia, we will work on germ free mice or use antimicrobial solution to modify the mouse skin microbiota.
Aim 3. Elucidate a mechanistic understanding of how the nymph and host skin microbiota modulate Borrelia burgdorferi transmission.
A. RNA Hi-Seq analysis of the guts of fed dysbiosed and normal ticks will be performed and genes/pathways significantly altered upon dysbiosis identified.
B. Genes significantly modulated by gut microbiota will be individually silenced in Borrelia infected nymphal ticks by RNAi and B. burgdorferi growth and migration in ticks and transmission to C3H/HeN mice assessed as in Aim 2.
This study will help us to understand the role of tick gut and host skin microbiota in the context of Lyme disease transmission and will likely identify new tick proteins that might serve as vaccine targets to prevent Borrelia growth and migration from the tick gut to the host skin – the essential prelude to transmission.

Wished skills: Person open to translational project : from cells, mouse to human.
Knowledge in biology (immunolgy, microbiology if possible.

Expertises which will be acquired during the training: Immunology, (Elisa, Western-Blot) ; Molecular biology (PCR, RT-PCR, sequencing, RNAI
Work with animals
Zxpertise acquired in immunology, infectiology and medical entomology.