Research Projects

Pore-forming toxins (PFTs) are abundant bacterial protein toxins that perforate host cell plasma membranes, leading to cell death. PFTs are considered one of nature's most proficient cell-killing entities. However, PFTs do not always act as non-specific killers, as they can also trigger complex cascades of programmed cell death (PCD) such as apoptosis, pyroptosis, and necroptosis. PCD pathways are crucial for host defense mechanisms, but pathogens can manipulate PCD-induction for their own benefits, such as nutrient acquisition, tissue invasion, and disease establishment. The activation of distinct PCD pathways in target cells in response to a specific PFT can shape the outcome of bacterial pathogenesis and host-pathogen interaction processes. Vibrio cholerae cytolysin (VCC), a prototype bacterial PFT secreted by the cholera pathogen Vibrio cholerae, is a potent virulence factor. VCC can induce apoptosis in target cells and elicit hallmark features of pyroptotic inflammatory cell death. This study aims to explore the mechanistic details of inflammatory cell death pathways generated in target cells in response to VCC and investigate whether this VCC-induced inflammatory cell death is connected to other forms of PCDs, such as apoptosis, in terms of evoking a PANoptotic inflammatory cell death response.