Mechanisms of Bartonella persistence in its reservoir host

Mécanismes de persistance de Bartonella dans son hôte réservoir

Hongkuan Deng (1)

1 BIPAR - Biologie moléculaire et immunologie parasitaires et fongiques

Each Bartonella species appears to be highly adapted to one or a limited number of reservoir hosts, in which it establishes a long-lasting intraerythrocytic bacteremia as the hallmark of infection. Although the course of Bartonella infection has been precisely described, the molecular mechanisms of host specific erythrocyte infection and the stages of precedent the arrival in the bloodstream are poorly understood. In this thesis we purposed to identify the mechanisms of erythrocyte infection by Bartonella and characterize the possible locations of Bartonella during the days before the intraerythrocytic stage.By the establishment of an in vitro model of adhesion and invasion of erythrocytes by Bartonella spp., we demonstrated that host specificity was determined by the interaction between bacteria and erythrocytes. By screening signature-tagged mutagenesis (STM) library of B. birtlesii in vivo and in vitro and ectopic expression, we revealed that type IV Trw locus was required for host-restricted adhesion to erythrocytes in a wide range of mammals. After that, we further characterized that only TrwJ1 and TrwJ2 were expressed and present on the surface of the bacteria and had the ability to bind to mouse erythrocytes, and the receptor of them was erythrocyte band3 by different technology (phage display, electron microscopy, far western blot and adherence and invasion inhibition assay). By the model of experimental infection of laboratory normal Balb/C mice and splenectomized mice with B. birtlesii, we showed that during the first 7 days, no bacteria were recovered from lymph nodes, bone marrow and brain, but in the spleen, transient in the liver, And bacteremia was the same in both infection models during the first 7 days, thereafter, bacteremia was 10 fold higher in splenectomized mice than in normal mice and lasted 2 weeks longer. This suggested that the spleen was able to retain Bartonella.In conclusion, the host specific adhesion between Bartonella and erythrocyte was mediated by Trw and erythrocytic band 3, and spleen had a role in retention Bartonella.

Pas de résumé français

Mots clés: Erythrocyte; Reservoir host; Bartonella

Mots clés: Hôte réservoir

Domaines: Sciences agricoles

Hongkuan Deng. Mécanismes de persistance de Bartonella dans son hôte réservoir. Sciences agricoles. Université Paris-Est, 2011. Français. ⟨NNT : 2011PEST0085⟩. ⟨tel-00734068⟩