Matches in SemOpenAlex for { <https://semopenalex.org/work/W1943485102> ?p ?o ?g. }
- W1943485102 abstract "Bartonella henselae (Bh) rarely shows any symptoms in its feline reservoir host but is responsible for a number of clinical outcomes during infection of the human incidental host. Bh shares with B. quintana (Bq) and B. bacilliformis (Bb) the remarkable capacity to induce tumour-like vascular proliferations. The study of Bartonella-host cell interactions might not only provide insides into the pathogenesis of Bh but might also serve as a model to investigate general mechanisms involved pathological angiogenesis, which is a hallmark of tumour growth. The Bh VirB/VirD4 type IV secretion system (T4SS) and the thereby translocated Bartonella-effector proteins (Beps) have been shown to be responsible for the subversion of a number of endothelial cell (EC) functions upon infection. This thesis aimed to elucidate the role of the VirB/VirD4/Bep system in Bh-triggered angioproliferation. The first chapter characterizes the Bh VirB T4SS translocated protein BepA as an effector mediating the inhibition of apoptosis in human umbilical vein endothelial cells (HUVECs). Either overexpressed in the effector-less ∆bepA-G mutant or ectopically expressed, BepA was sufficient to promote the anti-apoptotic activity. Delineation of BepA revealed that this activity is confined to the BID (Bep intracellular delivery) domain of BepA. Interestingly, only the homologue BepA2 (corresponding to the BID domain plus C-terminus of BepA) from Bq inhibited apoptosis as well. In contrast to Bh and Bq, B. tribocorum is not associated to vascular proliferation and its BepA-homologue did not show any anti-apoptotic activity. Upon translocation into the host cell BepA was targeted to the membrane. BepA-mediated anti-apoptosis correlated with an increase in cAMP and increased expression of cAMP-responsive genes, pointing to a mechanism involving the regulation of this second messenger. BepA not only inhibited chemically ActD-induced but also CTL-triggered apoptosis. Thus, BepA has the potential to play a role in vasoproliferation in an indirect way by enhancing cell survival. Chapter 2 presents a spheroid-based three-dimensional in vitro sprouting assay established to address the angiogenic potential of Bh. Compared to spheroids from uninfected HUVECs, spheroids from HUVECs pre-infected with Bh wild-type showed an increased sprouting activity, albeit sprout morphology was distinct from the sprouts induced by vascular endothelial growth factor (VEGF). Formation of those sprouts was in part VirB/Bep-dependent. Overexpressed BepA in the ∆bepA-G mutant strongly promoted sprout formation. Delineation of the domain required for this stimulation indicates parallels to the anti-apoptotic activity. BepD showed a moderate sprout-promoting effect. In contrary, BepG, involved in cytoskeletal rearrangement, displayed a potent interference with sprout formation. This novel in vitro model of Bh-triggered sprouting angiogenesis revealed distinct activities of the Beps in modulating sprout formation and contributing to the regulation of the Bh angiogenic activity in the course of the chronic vascular infection. In chapter 3 the effect of exogenous VEGF on Bh-infected ECs is addressed. VEGF is thought to be involved in Bh-induced vascular tumour formation by promoting EC proliferation in a paracrine manner. Assessing the biological activity of VEGF in assays such as proliferation, wound assay and capillary-like sprout formation revealed an intriguing interference of the VirB/VirD4/Bep system with responsiveness of infected ECs to stimulation with VEGF. Analysis of the VEGF receptor 2 pathways showed that Bh inhibited phosphorylation of tyrosine 1175. In Bh-infected ECs stimulated with VEGF, PLCγ1 was less recruited and phosphorylated and consequently downstream calcium flux and ERK1/2 activation were blocked. These data rather challenge the idea of a VEGF-driven paracrine loop in the presence of an active VirB/VirD4/Bep system and emphasize the modulatory role of the VirB T4SS balancing the angiogenic activity of Bh. The last chapter reports the role of the VirB/VirD4/Bep system in the paracrine-loop model of VEGF production. HeLa cells produced VEGF upon exposure to Bh in a VirB/Bep-dependent manner. BepD elicited a strong stimulation of VEGF secretion in HeLa cells when overexpressed in the ∆bepB-G mutant. A shift in colour of the cell culture supernatant, depending on the cell culture media used, was associated to VirB T4SS translocation activity but not particularly to VEGF production. The shift probably is due to acidification of the supernatant. Hence, in addition to the previously reported BadA also the VirB/VirD4/Bep system, especially BepD, independently is able to trigger the production of an essential regulator of angiogenesis." @default.
- W1943485102 created "2016-06-24" @default.
- W1943485102 creator A5042055652 @default.
- W1943485102 date "2009-01-01" @default.
- W1943485102 modified "2023-09-26" @default.
- W1943485102 title "The role of the VirB/VirD4/Bep system in Bartonella henselae-triggered vascular proliferation" @default.
- W1943485102 cites W1531339633 @default.
- W1943485102 cites W1560280373 @default.
- W1943485102 cites W1572252257 @default.
- W1943485102 cites W1835091344 @default.
- W1943485102 cites W1866448649 @default.
- W1943485102 cites W1937595028 @default.
- W1943485102 cites W1968541721 @default.
- W1943485102 cites W1968719918 @default.
- W1943485102 cites W1972520421 @default.
- W1943485102 cites W1975106447 @default.
- W1943485102 cites W1975670140 @default.
- W1943485102 cites W1977644290 @default.
- W1943485102 cites W1977834935 @default.
- W1943485102 cites W1978216501 @default.
- W1943485102 cites W1981683660 @default.
- W1943485102 cites W1981783746 @default.
- W1943485102 cites W1983767314 @default.
- W1943485102 cites W1987226377 @default.
- W1943485102 cites W1999095014 @default.
- W1943485102 cites W2000276122 @default.
- W1943485102 cites W2000292756 @default.
- W1943485102 cites W2000444833 @default.
- W1943485102 cites W2006254842 @default.
- W1943485102 cites W2013134124 @default.
- W1943485102 cites W2023096047 @default.
- W1943485102 cites W2025794715 @default.
- W1943485102 cites W2029391105 @default.
- W1943485102 cites W2030224529 @default.
- W1943485102 cites W2033604879 @default.
- W1943485102 cites W2038248457 @default.
- W1943485102 cites W2040278047 @default.
- W1943485102 cites W2043697833 @default.
- W1943485102 cites W2048215059 @default.
- W1943485102 cites W2048455227 @default.
- W1943485102 cites W2049773528 @default.
- W1943485102 cites W2059668632 @default.
- W1943485102 cites W2061421066 @default.
- W1943485102 cites W2068877244 @default.
- W1943485102 cites W2070443775 @default.
- W1943485102 cites W2076009833 @default.
- W1943485102 cites W2076796449 @default.
- W1943485102 cites W2078254281 @default.
- W1943485102 cites W2078516718 @default.
- W1943485102 cites W2078738962 @default.
- W1943485102 cites W2079449263 @default.
- W1943485102 cites W2082667221 @default.
- W1943485102 cites W2082876993 @default.
- W1943485102 cites W2083227510 @default.
- W1943485102 cites W2088359631 @default.
- W1943485102 cites W2089594628 @default.
- W1943485102 cites W2094026979 @default.
- W1943485102 cites W2097165693 @default.
- W1943485102 cites W2107702121 @default.
- W1943485102 cites W2109985652 @default.
- W1943485102 cites W2115390024 @default.
- W1943485102 cites W2115410765 @default.
- W1943485102 cites W2118744456 @default.
- W1943485102 cites W2120552228 @default.
- W1943485102 cites W2120673613 @default.
- W1943485102 cites W2122104710 @default.
- W1943485102 cites W2122301597 @default.
- W1943485102 cites W2127135538 @default.
- W1943485102 cites W2128635872 @default.
- W1943485102 cites W2128664946 @default.
- W1943485102 cites W2130397039 @default.
- W1943485102 cites W2147812298 @default.
- W1943485102 cites W2149990334 @default.
- W1943485102 cites W2170107782 @default.
- W1943485102 cites W2171149491 @default.
- W1943485102 cites W2189729969 @default.
- W1943485102 cites W2294836073 @default.
- W1943485102 cites W2311972351 @default.
- W1943485102 cites W2411239681 @default.
- W1943485102 cites W2470223656 @default.
- W1943485102 doi "https://doi.org/10.5451/unibas-004872344" @default.
- W1943485102 hasPublicationYear "2009" @default.
- W1943485102 type Work @default.
- W1943485102 sameAs 1943485102 @default.
- W1943485102 citedByCount "0" @default.
- W1943485102 crossrefType "dissertation" @default.
- W1943485102 hasAuthorship W1943485102A5042055652 @default.
- W1943485102 hasConcept C190283241 @default.
- W1943485102 hasConcept C202751555 @default.
- W1943485102 hasConcept C2777411675 @default.
- W1943485102 hasConcept C2777834122 @default.
- W1943485102 hasConcept C2780394083 @default.
- W1943485102 hasConcept C49039625 @default.
- W1943485102 hasConcept C502942594 @default.
- W1943485102 hasConcept C51785407 @default.
- W1943485102 hasConcept C54355233 @default.
- W1943485102 hasConcept C55493867 @default.
- W1943485102 hasConcept C62112901 @default.
- W1943485102 hasConcept C86803240 @default.
- W1943485102 hasConcept C95444343 @default.