title: Bartonella henselae trimeric autotransporter adhesin BadA expression interferes with effector translocation by the VirB/D4 type IV secretion system.
abstract: The Gram-negative, zoonotic pathogen Bartonella henselae is the aetiological agent of cat scratch disease, bacillary angiomatosis and peliosis hepatis in humans. Two pathogenicity factors of B. henselae - each displaying multiple functions in host cell interaction - have been characterized in greater detail: the trimeric autotransporter Bartonella adhesin A (BadA) and the type IV secretion system VirB/D4 (VirB/D4 T4SS). BadA mediates, e.g. binding to fibronectin (Fn), adherence to endothelial cells (ECs) and secretion of vascular endothelial growth factor (VEGF). VirB/D4 translocates several Bartonella effector proteins (Beps) into the cytoplasm of infected ECs, resulting, e.g. in uptake of bacterial aggregates via the invasome structure, inhibition of apoptosis and activation of a proangiogenic phenotype. Despite this knowledge of the individual activities of BadA or VirB/D4 it is unknown whether these major virulence factors affect each other in their specific activities. In this study, expression and function of BadA and VirB/D4 were analysed in a variety of clinical B. henselae isolates. Data revealed that most isolates have lost expression of either BadA or VirB/D4 during in vitro passages. However, the phenotypic effects of coexpression of both virulence factors was studied in one clinical isolate that was found to stably coexpress BadA and VirB/D4, as well as by ectopic expression of BadA in a strain expressing VirB/D4 but not BadA. BadA, which forms a dense layer on the bacterial surface, negatively affected VirB/D4-dependent Bep translocation and invasome formation by likely preventing close contact between the bacterial cell envelope and the host cell membrane. In contrast, BadA-dependent Fn binding, adhesion to ECs and VEGF secretion were not affected by a functional VirB/D4 T4SS. The obtained data imply that the essential virulence factors BadA and VirB/D4 are likely differentially expressed during different stages of the infection cycle of Bartonella.
authors.affiliation: Focal Area Infection Biology, Biozentrum of the University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: Yun-Yueh
authors.initials: YY
authors.lastname: Lu
authors.forename: Bettina
authors.initials: B
authors.lastname: Franz
authors.forename: Matthias C
authors.initials: MC
authors.lastname: Truttmann
authors.forename: Tanja
authors.initials: T
authors.lastname: Riess
authors.forename: Jérémie
authors.initials: J
authors.lastname: Gay-Fraret
authors.forename: Marco
authors.initials: M
authors.lastname: Faustmann
authors.forename: Volkhard A J
authors.initials: VA
authors.lastname: Kempf
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehio
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D018416:Bartonella henselae / Q000235:genetics* / Q000472:pathogenicity; D002372:Cat-Scratch Disease / Q000378:metabolism / Q000382:microbiology*; D002415:Cats / Q000382:microbiology*; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D011485:Protein Binding; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D037521:Virulence Factors