Bacterial Pore-forming Toxins: Structure-function Studies in the Context of Host-Pathogen Interaction Processes and Immunobiology


                                                                                                                                                                                                                                                                                             
Dr. Kausik Chattopadhyay
Associate Professor
Centre for Protein Science, Design and Engineering
Department of Biological Sciences
Indian Institute of Science Education and Research (IISER) Mohali
(Lab- 3L2/Office- 3F3)
Sector 81, SAS Nagar, Mohali, Punjab 140306, India.

E-mail: 
kausik[at]iisermohali.ac.in
                                                                                                                                                                                                        




News:

-11th International Symposium on Cell Surface Macromolecules (11th ISCSM) at IISER Mohali, 24-28 February 2017.

-Dr. Kausik Chattopadhyay has been selected as the recipient of DBT National BioScience Award for Career Development 2014.

-The lab is now part of the Centre for Protein Science, Design and Engineering (CPSDE), at the Department of Biological Sciences, IISER Mohali. The CPSDE at IISER Mohali  has been set up by funding from the Ministry of Human Resource Development (MHRD), Government of India, under its Centre of Excellence(COE)-FAST programme.


Recent publications from the lab:
  1. Kathuria, R., Mondal, A. K., Sharma, R., Bhattacharyya, S., and Chattopadhyay, K. (2018) Revisiting the role of cholesterol in regulating the pore-formation mechanism of Vibrio cholerae cytolysin,a membrane-damaging ß-barrel pore-forming toxin. Biochemical Journal 475 (19), 3039-3055.
  2. Kathuria R, and Chattopadhyay K. (2018) Vibrio cholerae cytolysin:Multiple facets of the membrane interaction mechanism of a β-barrelpore-forming toxin. IUBMB Life. 70(4): 260-266. [This review article was selected for the issue highlight].
  3. Kundu, N., Tichkule, S., Pandit, S. B., and Chattopadhyay, K. (2017) Disulphide bond restrains C-terminal Region of thermostable direct hemolysin during folding to promote oligomerization. Biochemical Journal 474 (2), 317-331.
  4. Rai, A. K., and Chattopadhyay, K. (2016) Revisiting the oligomerization mechanism of Vibrio cholerae cytolysin, a beta-barrel pore-forming toxin. Biochem. Biophys. Res. Com., 474 (3), 421-427.
  5. Khilwani, B., and Chattopadhyay, K. (2015) Signaling beyond punching holes: modulation of cellular responses by Vibrio cholerae cytolysin. Toxins, 7(8), 3344-3358.
  6. Rai. A. K., Kundu, N., and Chattopadhyay, K. (2015) Physicochemical constraints of elevated pH affect efficient membrane interaction and arrest an abortive membrane-bound oligomeric intermediate of the beta-barrel pore-forming toxin Vibrio cholerae cytolysin. Archives of Biochemistry and Biophysics. 583, 9-17.
  7. Rai, A. K., and Chattopadhyay, K. (2015) Revisiting the membrane interaction mechanism of a membrane-damaging β-barrel pore-forming toxin Vibrio cholerae cytolysin. Molecular Microbiology, 97(6), 1051-1062.
  8. Lata, K., and Chattopadhyay, K. (2015) Helicobacter pylori TlyA Forms Amyloid-like Aggregates with Potent Cytotoxic Activity. Biochemistry, 54 (23), 3649-3659.
  9. Khilwani, B., Mukhopadhaya, A.*, and Chattopadhyay, K.* (2015) Transmembrane Oligomeric form of Vibrio cholerae Cytolysin Triggers TLR2/TLR6-dependent Pro-inflammatory Responses in Monocytes and Macrophages. Biochemical Journal, 466 (1), 147-161. [*Joint Corresponding Authors]
  10. Rai, A. K., and Chattopadhyay, K. (2015) Vibrio cholerae cytolysin: structure-function mechanism of an atypical β-barrel pore-forming toxin. Adv. Exp. Med. Biol, 842, 109-125.
  11. Lata, K. and Chattopadhyay, K. (2014) Helicobacter pylori TlyA agglutinates liposomes, and induces fusion and permeabilization of the liposome membranes. Biochemistry, 53 (22), 3553-3563.
  12. Rai, A. K., and Chattopadhyay, K. (2014) Trapping of Vibrio cholerae Cytolysin in the Membrane-bound Monomeric State Blocks Membrane Insertion and Functional Pore Formation by the Toxin. J. Biol. Chem, 289 (24), 16978-16987.
  13. Lata, K, Paul, K., and Chattopadhyay, K. (2014) Functional characterization of Helicobacter pylori TlyA: Pore-forming hemolytic activity and cytotoxic property of the protein. Biochem. Biophys. Res. Com., 444 (2), 153-157.
  14. Paul, K. and Chattopadhyay, K. (2014) Pre-pore oligomer formation by Vibrio cholerae cytolysin: Insights from a truncated variant lacking the pore-forming pre-stem loop. Biochem. Biophys. Res. Com., 443 (1), 189-193.
  15. Rai, A. K.*, Paul, K.*, and Chattopadhyay, K. (2013) Functional mapping of the lectin activity site on the β-Prism domain of Vibrio cholerae cytolysin: implications for the membrane pore-formation mechanism of the toxin. J. Biol. Chem, 288 (3), 1665-1673. (*These authors contributed equally to this work)
  16. Paul, K. and Chattopadhyay, K. (2012) Single point mutation in Vibrio cholerae cytolysin compromises membrane pore-formation mechanism of the toxin. FEBS Journal, 279 (21), 4039-4051.
  17. Paul, K. and Chattopadhyay, K. (2011) Unfolding distinguishes the Vibrio cholerae cytolysin precursor from the mature form of the toxin. Biochemistry, 50 (19), 3936-3945.

Ongoing Research Interest:


Structure-Function Studies on Pore-Forming Protein Toxins.
Pore-forming protein toxins (PFTs) represent a special class of membrane damaging cytolytic proteins, and they are found in wide spectrum of organisms ranging from bacteria to humans. They exert their toxic effects by punching 'holes' into target cell membrane, thus destroying the natural permeability barrier function of the cell membrane. PFTs are, in general, synthesized as water-soluble monomeric molecules, and in contact with target cell membranes they form membrane-inserted oligomeric pores. However, in spite of sharing this overall general scheme, PFTs differ significantly from each other in the intricate details of their pore formation mechanisms. A major mechanistic challenge associated with the membrane pore formation process by PFTs is elucidating the folding pathways that ensure thermodynamic compatibility of the water-soluble monomeric and the membrane-inserted oligomeric form of the toxin with aqueous and lipid milieu, respectively. One of the major research interests of my group is focused on studying structure-function relationship of some of the prominent bacterial PFTs. The critical issues we address are:
1. Mechanistic details of oligomeric membrane channel formation by PFTs.
2. Mechanism(s) associated with cellular responses triggered by PFTs.

 

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