Vibrio cholerae GbpA elicits necrotic cell death in intestinal cells.

Vibrio choleraeN-acetylglucosamine-binding protein GbpA is a secretory protein that facilitates the initial adherence of bacteria in the human intestine. Until now, considerable progress in the characterization of GbpA has been done, yet little is known about its role in host response. Our present studies demonstrated that GbpA at the amount secreted in the intestine resulted in decreased cell viability, altered cell morphology, disruption of cell membrane integrity and damage of cellular DNA indicating necrotic cell death. We observed that GbpA exposure leads to mitochondrial dysfunction, characterized by accumulation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential and depletion of ATP pool in host cells. Additionally, the intra-cellular ROS, accumulated in response to GbpA, were found to induce the migration of NF-κB from cytoplasm into nucleus in host cells. Taken together, these results prompted us to conclude that GbpA orchestrates a necrotic response in host cells which may have implications in immune response.