title: Heterogeneity of Borrelia burgdorferi Sensu Stricto Population and Its Involvement in Borrelia Pathogenicity: Study on Murine Model with Specific Emphasis on the Skin Interface.
abstract: Lyme disease is a multisystemic disorder caused by B. burgdorferi sl. The molecular basis for specific organ involvement is poorly understood. The skin plays a central role in the development of Lyme disease as the entry site of B. burgdorferi in which specific clones are selected before dissemination. We compared the skin inflammatory response (antimicrobial peptides, cytokines and chemokines) elicited by spirochete populations recovered from patients presenting different clinical manifestations. Remarkably, these spirochete populations induced different inflammatory profiles in the skin of C3H/HeN mice. As spirochete population transmitted into the host skin is heterogeneous, we isolated one bacterial clone from a population recovered from a patient with neuroborreliosis and compared its virulence to the parental population. This clone elicited a strong cutaneous inflammatory response characterized by MCP-1, IL-6 and antimicrobial peptides induction. Mass spectrometry of this clone revealed 110 overexpressed proteins when compared with the parental population. We further focused on the expression of nine bacterial surface proteins. bb0347 coding for a protein that interacts with host fibronectin, allowing bacterial adhesion to vascular endothelium and extracellular matrix, was found to be induced in host skin with another gene bb0213 coding for a hypothetical protein. These findings demonstrate the heterogeneity of the B. burgdorferi ss population and the complexity of the interaction involved early in the skin.
authors.affiliation: EA7290: Virulence bactérienne précoce: groupe Borréliose de Lyme, Facultés de médecine et de pharmacie, Université de Strasbourg, Strasbourg, France; Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kern
authors.affiliation: Laboratoire de Spectrométrie de Masse BioOrganique, Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, CNRS, UMR7178, Strasbourg, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Schnell
authors.affiliation: EA7290: Virulence bactérienne précoce: groupe Borréliose de Lyme, Facultés de médecine et de pharmacie, Université de Strasbourg, Strasbourg, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Bernard
authors.affiliation: Laboratoire de Spectrométrie de Masse BioOrganique, Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, CNRS, UMR7178, Strasbourg, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Bœuf
authors.affiliation: EA7290: Virulence bactérienne précoce: groupe Borréliose de Lyme, Facultés de médecine et de pharmacie, Université de Strasbourg, Strasbourg, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Jaulhac
authors.affiliation: EA7290: Virulence bactérienne précoce: groupe Borréliose de Lyme, Facultés de médecine et de pharmacie, Université de Strasbourg, Strasbourg, France.
authors.forename: Elody
authors.initials: E
authors.lastname: Collin
authors.affiliation: EA7290: Virulence bactérienne précoce: groupe Borréliose de Lyme, Facultés de médecine et de pharmacie, Université de Strasbourg, Strasbourg, France.
authors.forename: Cathy
authors.initials: C
authors.lastname: Barthel
authors.affiliation: Laboratoire de Spectrométrie de Masse BioOrganique, Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, CNRS, UMR7178, Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ehret-Sabatier
authors.affiliation: EA7290: Virulence bactérienne précoce: groupe Borréliose de Lyme, Facultés de médecine et de pharmacie, Université de Strasbourg, Strasbourg, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boulanger
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000235:genetics* / Q000472:pathogenicity; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005408:Flagellin / Q000235:genetics / Q000378:metabolism; D018740:Genetic Heterogeneity; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D064307:Microbiota; D012867:Skin / Q000378:metabolism / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005353:Fibronectins; D015850:Interleukin-6; D005408:Flagellin