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Bartonella bacilliformis GroEL: Effect on Growth of Human Vascular Endothelial Cells in Infected Cocultures
Division of Biological Sciences, University of Montana, Missoula, Montana 59812, USA
Address for correspondence: Michael F. Minnick, Division of Biological Sciences, 32 Campus Drive #4824, University of Montana, Missoula, MT 59812-4824. Voice: 406-243-5972; fax: 406-243-4184. mike.minnick{at}mso.umt.edu.
Bartonella are the only bacteria known to induce angioproliferative lesions of the human vasculature and liver during infection. Previous work from our lab suggests that GroEL participates in the mitogenic response observed in HUVEC cultures supplemented with the soluble fraction of Bartonella bacilliformis. Work in this study shows that exposure to high concentrations of the fraction is actually cytotoxic for HUVECs. To analyze this phenomenon, live B. bacilliformis-HUVEC cocultures were employed to study the effect of excess bacterial GroEL on the host cell during active infection. Four B. bacilliformis strains were generated to produce varying levels of GroEL. HUVEC cocultures with LSS100, a strain that synthesizes markedly greater quantities of GroEL relative to others, significantly accelerates apoptosis of the cocultured HUVECs relative to other strains. Acceleration of apoptosis can be inhibited by Z-VAD-FMK, a pan-caspase inhibitor. Time course data show that, at 18 h of infection, both LSS100 and control strains significantly inhibit spontaneous apoptosis of cocultured HUVECs, as previously reported for other Bartonella species. However, by 48 h, LSS100 significantly increases apoptosis of the host cell. We hypothesize that intracellular Bartonella GroEL functions as an Hsp60 analogue, a eukaryotic orthologue known to accelerate pro-caspase 3 activation by enhancing its vulnerability to upstream activator caspases. These data suggest another strategy whereby Bartonella may regulate host cell growth.
Key Words: Bartonella • GroEL • apoptosis • endothelial cells
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