Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation
Version of Record online: 12 MAR 2009
© 2009 Blackwell Publishing Ltd
Volume 11, Issue 7, pages 1088–1101, July 2009
How to Cite
Scheidegger, F., Ellner, Y., Guye, P., Rhomberg, T. A., Weber, H., Augustin, H. G. and Dehio, C. (2009), Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation. Cellular Microbiology, 11: 1088–1101. doi: 10.1111/j.1462-5822.2009.01313.x
- Issue online: 2 JUN 2009
- Version of Record online: 12 MAR 2009
- Received 30 September, 2008; revised 24 February, 2009; accepted 27 February, 2009.
The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.