Research

Life Sciences & Biotechnology

Title :

Study of inflammatory cell death mechanism induced by the pore-forming toxin Vibrio cholerae cytolysin and its implication for the cell-killing pathophysiological function of the toxin

Area of research :

Life Sciences & Biotechnology

Focus area :

Cell Death Mechanisms, Bacterial Pathogenesis

Principal Investigator :

Prof. Kausik Chattopadhyay, Indian Institute Of Science Education And Research (IISER) Mohali, Punjab

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Details

Executive Summary :

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.

Co-PI:

Prof. Arunika Mukhopadhaya, Indian Institute Of Science Education And Research (IISER) Mohali, Punjab-140306

Total Budget (INR):

61,96,054

Organizations involved