Intracellular Induction of the
            <i>Bartonella henselae virB</i>
            Operon by Human Endothelial Cells

Schmiederer, Michael; Arcenas, Rodney; Widen, Raymond; Valkov, Nikola; Anderson, Burt

doi:10.1128/iai.69.10.6495-6502.2001

Cited by 38 publications

(23 citation statements)

References 42 publications

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“…The ⌬batR strain contains an in-frame deletion of 678 bp in batR, resulting in a 45-bp cryptic open reading frame composed of 5Ј and 3Ј sequences of batR. To generate the batR complementation plasmid pbatR, a 782-bp fragment containing batR and the Shine-Dalgarno sequence of pPG110 was amplified using primers prIT009 (47) and the 333-bp intergenic upstream region of the bepD gene were amplified using primers prIT011-prIT012 and prIT015-prIT016, respectively. The terminal EcoRI and BamHI sites were used to insert the fragment in the corresponding sites of pCD366, yielding pPvirB-gfp and pPbepD-gfp.…”

Section: Methodsmentioning

confidence: 99%

The BatR/BatS Two-Component Regulatory System Controls the Adaptive Response ofBartonella henselaeduring Human Endothelial Cell Infection

et al. 2010

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Here, we report the first comprehensive study of Bartonella henselae gene expression during infection of human endothelial cells. Expression of the main cluster of upregulated genes, comprising the VirB type IV secretion system and its secreted protein substrates, is shown to be under the positive control of the transcriptional regulator BatR. We demonstrate binding of BatR to the promoters of the virB operon and a substrate-encoding gene and provide biochemical evidence that BatR and BatS constitute a functional twocomponent regulatory system. Moreover, in contrast to the acid-inducible (pH 5.5) homologs ChvG/ChvI of Agrobacterium tumefaciens, BatR/BatS are optimally activated at the physiological pH of blood (pH 7.4). By conservation analysis of the BatR regulon, we show that BatR/BatS are uniquely adapted to upregulate a genus-specific virulence regulon during hemotropic infection in mammals. Thus, we propose that BatR/BatS two-component system homologs represent vertically inherited pH sensors that control the expression of horizontally transmitted gene sets critical for the diverse host-associated life styles of the alphaproteobacteria.

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Section: Methodsmentioning

confidence: 99%

The BatR/BatS Two-Component Regulatory System Controls the Adaptive Response ofBartonella henselaeduring Human Endothelial Cell Infection

et al. 2010

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“…B. henselae 882str, a streptomycin-resistant laboratory-adapted strain of ATCC 49882 (25), was grown on streptomycin (200 g/ml) chocolate agar. A green fluorescent protein (GFP)-expressing derivative of 882str was previously developed in our laboratory by transformation with plasmid pVBGFPF (39) and was grown on kanamycin (25 g/ml) chocolate agar. The B. henselae virB promoter used to drive the expression of the gfp gene in pVBGFPF is activated intracellularly (39).…”

Section: Methodsmentioning

confidence: 99%

“…A green fluorescent protein (GFP)-expressing derivative of 882str was previously developed in our laboratory by transformation with plasmid pVBGFPF (39) and was grown on kanamycin (25 g/ml) chocolate agar. The B. henselae virB promoter used to drive the expression of the gfp gene in pVBGFPF is activated intracellularly (39). For certain experiments, bacteria were heat killed at 100°C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Induction of a Potential Paracrine Angiogenic Loop between Human THP-1 Macrophages and Human Microvascular Endothelial Cells duringBartonella henselaeInfection

et al. 2002

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Bartonella henselae is responsible for various disease syndromes that loosely correlate with the immune status of the host. In the immunocompromised individual, B. henselae-induced angiogenesis, or bacillary angiomatosis, is characterized by vascular proliferative lesions similar to those in Kaposi's sarcoma. We hypothesize that B. henselae-mediated interaction with immune cells, namely, macrophages, induces potential angiogenic growth factors and cytokines which contribute in a paracrine manner to the proliferation of endothelial cells. Vascular endothelial growth factor (VEGF), a direct inducer of angiogenesis, and interleukin-1␤ (IL-1␤), a potentiator of VEGF, were detected within 12 and 6 h, respectively, in supernatants from phorbol 12-myristate 13-acetate-differentiated human THP-1 macrophages exposed to live B. henselae. Pretreatment of macrophages with cytochalasin D, a phagocytosis inhibitor, yielded comparable results, suggesting that bacterium-cell attachment is sufficient for VEGF and IL-1␤ induction. IL-8, an angiogenic cytokine with chemotactic properties, was induced in human microvascular endothelial cells (HMEC-1) within 6 h of infection, whereas no IL-8 induction was observed in infected THP-1 cells. In addition, conditioned medium from infected macrophages induced the proliferation of HMEC-1, thus demonstrating angiogenic potential. These data suggest that Bartonella modulation of host or target cell cytokines and growth factors, rather than a direct role of the bacterium as an endothelial cell mitogen, is the predominant mechanism responsible for angiogenesis. B. henselae induction of VEGF, IL-1␤, and IL-8 outlines a broader potential paracrine angiogenic loop whereby macrophages play the predominant role as the effector cell and endothelial cells are the final target cell, resulting in their proliferation.

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“…They bear Walker A (motif I) and B (motif II or DExx box) NTP-binding sequences [88] and may use the energy of Rhizobium etli bacterium; N2-fixation [154] Sinorhizobium meliloti bacterium; N2-fixation [14,15,17] Shigella flexneri plasmid ColIb P9 bacterium; diarrhoea / dysentery [155] Bartonella henselae and tribocorum bacterium; cat scratch disease, bacteremia [156][157][158][159][160] Campylobacter jejuni bacterium; bacterial diarrhoea [161,162] Toxoplasma gondii protozoon; toxoplasmosis (encephalitis) [54] Leishmania donovani protozoon; leishmaniasis [54] Mycobacterium tuberculosis bacterium; tuberculosis [54] Bordetella bronchiseptica bacterium; bronchitis [14,15,17] Enterobacter aerogenes bacterium; nosocomial infections [11] Actinobacillus actinomycetemcomitans bacterium; periodontitis [14,15,17,163,164] Escherichia coli bacterium; diarrhea [11] Caulobacter crescentus bacterium; non-pathogenic [14,15,17] Coxiella burnetii bacterium; acute febrile disease, endocarditis, pneumonitis [165,166] Thiobacillus ferroxidans bacterium; iron oxidation [14,15,17] Wolbachia intracellular symbiont of arthropods; sexual alterations in host [167,168] Ralstonia eutrophantus bacterium; heavy-metal resistance [11,169] Salmonella typhi, typhimurium and enteriditis bacterium; typhus, salmonellosis …”

Section: Transfer Factors In Conjugative Type-iv Secretionmentioning

confidence: 99%

Coupling Factors in Macromolecular Type-IV Secretion Machineries

Gomis‐Rüth

Sola

Cruz³

et al. 2004

CPD

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Type IV secretion systems (T4SSs) are bacterial multiprotein organelles specialised in the transfer of (nucleo)protein complexes across cell membranes. They are essential for conjugation, bacterial-induced tumour formation in plant cells, as observed in Agrobacterium, toxin secretion, like in Bordetella and Helicobacter, cell-to-cell translocation of virulence factors, and intracellular activity of mammalian pathogens like Legionella. By enabling conjugative DNA delivery, these systems contribute to the spread of antibiotic resistance genes among bacteria. These translocons are made up by 10-15 proteins that are analogous to Vir proteins of Agrobacterium and traverse both membranes and the periplasmic space in between in Gram-negative bacteria. Their secretion substrates range from single-stranded DNA / protein complexes to multicomponent toxins and they are assisted by integral inner-membrane coupling factors, the multimeric type-IV coupling proteins (T4CPs), to connect the macromolecular complexes to be transferred with the secretory conduit. To do so, these T4CPs may be required to localise close to the secretion machinery within the donor cell. The T4CP structural prototype is the hexameric protein TrwB of Escherichia coli conjugative plasmid R388, closely related to Agrobacterium VirD4 protein. It is responsible for coupling the relaxosome with the DNA transport apparatus during cell mating. T4CP family members are related to SpoIIIE/FtsK proteins, essential for DNA pumping during sporulation and cell division. These features suggest possible mechanisms for conjugal T4CP function: as a simple coupler between two molecular machines, as a rotating device to pump DNA through the type-IV transport pore, or as a DNA injector, whereby its central channel would function as part of the transport pore.

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Intracellular Induction of the Bartonella henselae virB Operon by Human Endothelial Cells

Cited by 38 publications

References 42 publications

The BatR/BatS Two-Component Regulatory System Controls the Adaptive Response ofBartonella henselaeduring Human Endothelial Cell Infection

The BatR/BatS Two-Component Regulatory System Controls the Adaptive Response ofBartonella henselaeduring Human Endothelial Cell Infection

Induction of a Potential Paracrine Angiogenic Loop between Human THP-1 Macrophages and Human Microvascular Endothelial Cells duringBartonella henselaeInfection

Coupling Factors in Macromolecular Type-IV Secretion Machineries

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