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New insights into the infection strategy of lineage 3 and lineage 4 Bartonella species

Barbier, Clément. New insights into the infection strategy of lineage 3 and lineage 4 Bartonella species. 2019, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_13513

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Abstract

The α-proteobacterial genus Bartonella comprises Gram negative facultative intracellular pathogens causing a long-lasting intraerythrocytic infection in their specific mammalian host. Bartonella spp. are divided in 4 different lineages according to the nature of the virulence factors involved during the infection process. Studies on lineage 4 species revealed the involvement of two type 4 secretion systems (T4SS) for the establishment of a successful infection process: The VirB/D4 T4SS and Trw T4SS. The VirB/D4 T4SS contributes to Bartonella pathogenicity by translocating proteins called Bartonella effector proteins (Bep) during the dermal stage of the infection. The Trw T4SS is engaged during the blood stage triggering erythrocytes colonization and determine the host-specificity.
In this study, we focus our researches on one hand on the role in vivo of the VirB/D4 and its effectors during Bartonella tribocorum infection. On the other hand, we establish an in vivo infection model for lineage 3 by using Bartonella 1-1C.
Investigations on the role in vivo of the VirB/D4 T4SS during the infection process of B. tribocorum revealed a bacteremic phenotype of the full bep mutant Btr ΔbepA-I. Since bep were assumed essential for infection, this unexpected result pushed us to call into question the central role of these effectors. Phylogenetic analysis combined with in vivo infections revealed the translocation via the VirB/D4 T4SS of an additional effector named YopJ. Firstly described as a Type 3 secretion effector in Yersinia Pestis and based on our results, we hypnotize that YopJ in Bartonella species evolved as a Type 4 secretion effector. This new insight concerning Bartonella leads to a new way of approaching infection process of Bartonella species.
Since Lineage 3 species harbor a flagella instead of a Trw T4SS and translocate a different cocktails of Bep compared to lineage 4 we analyzed the in vivo infection cycle of this lineage. Investigations on the lineage 3 strain B 1-1C allowed the establishment of an intravenous (i.v.) and intradermal (i.d.) in vivo infection model in rat. One hallmark of Bartonella infection is the persistent intraerythrocytic bacteremia. In this study, we show that B 1-1C does not colonize erythrocytes. Results obtained during this report pushed us to reconsider rat as the specific mammalian host of B 1-1C.
Advisors:Dehio, Christoph and De Bolle, Xavier
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Dehio, Christoph
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13513
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (V, 99 Seiten)
Language:English
Identification Number:
Last Modified:18 Feb 2020 05:30
Deposited On:17 Feb 2020 15:42

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