title: The Trw type IV secretion system of Bartonella mediates host-specific adhesion to erythrocytes.
abstract: Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The alpha-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage to facilitate host-restricted adhesion to erythrocytes in a wide range of mammals.
authors.affiliation: Unité Sous Contrat Bartonella, INRA, Maisons-Alfort, France. mvayssier@vet-alfort.fr
authors.forename: Muriel
authors.initials: M
authors.lastname: Vayssier-Taussat
authors.forename: Danielle
authors.initials: D
authors.lastname: Le Rhun
authors.forename: Hong Kuan
authors.initials: HK
authors.lastname: Deng
authors.forename: Francis
authors.initials: F
authors.lastname: Biville
authors.forename: Sandra
authors.initials: S
authors.lastname: Cescau
authors.forename: Antoine
authors.initials: A
authors.lastname: Danchin
authors.forename: Geneviève
authors.initials: G
authors.lastname: Marignac
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lenaour
authors.forename: Henri Jean
authors.initials: HJ
authors.lastname: Boulouis
authors.forename: Maria
authors.initials: M
authors.lastname: Mavris
authors.forename: Lionel
authors.initials: L
authors.lastname: Arnaud
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Maxime
authors.initials: M
authors.lastname: Quebatte
authors.forename: Philipp
authors.initials: P
authors.lastname: Engel
authors.forename: Henri
authors.initials: H
authors.lastname: Saenz
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehio
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D001473:Bartonella / Q000378:metabolism*; D001474:Bartonella Infections / Q000382:microbiology*; D002415:Cats; D002448:Cell Adhesion; D004912:Erythrocytes / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors