Prof. Kausik Chattopadhyay's Lab: Cytolysin Study Group at IISER Mohali

Pore-Forming Toxins

Structure-Function Studies in the Context of Host-Pathogen Interaction and Immunity

Prof. Kausik Chattopadhyay, PhD, FNASc, FRSB

Department of Biological Sciences

Indian Institute of Science Education and Research Mohali

IISER Mohali, Sector 81, SAS Nagar, Mohali, Punjab 140306, India.

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

Editorial Board Member of Journal of Bacteriology (American Society for Microbiology, ASM)

Academic Editor, in the Editorial Board of PLOS Pathogens

PhD and post-doctoral research opportunity: in the area of biochemistry/cell-biology/immunobiology of pore-forming protein toxins.

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Highlights:

-Dr. Kausik Chattopadhyay is the recipient of the “C. R. Krishna Murti Award” of Society of Biological Chemists (India) for the year 2021 for his contributions in the field of Biochemistry and Allied Sciences.

-Dr. Kausik Chattopadhyay is elected as a Fellow of National Academy of Sciences, India (NASI) in the year 2019.

-Book volume co-edited by Dr. Kausik Chattopadhyay: Biochemical and Biophysical Roles of Cell Surface Molecules to by published by Springer in the series Advances in Experimental Medicine and Biology.

-"Interdisciplinary research: personal memoir of a biochemist" by Kausik Chattopadhyay.

-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.

Research Interest of Our Lab: 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.

Notable Publications from the Lab:

Gandhi S, Puravankara S, Mondal AK, Chauhan A, Yadav SP, Chattopadhyay K*, Mukhopadhaya A* (2025) Vibrio cholerae cytolysin induces pro-inflammatory and death signals through novel TLR assembly. PLOS Pathogens. 21(4):e1013033. doi: 10.1371/journal.ppat.1013033. Online ahead of print.
Lata K, Nandy K, Geetika, Chattopadhyay K* (2025) Mechanistic Cooperation of the Two Pore-Forming Transmembrane Motifs Regulates the β-Barrel Pore Formation by Listeriolysin O. Biochemistry. 64(4):917-927. doi: 10.1021/acs.biochem.4c00592.
Chatterjee S, Gupta T, Kaur G, Chattopadhyay* (2024) Pyroptotic executioner pore-forming protein gasdermin D forms oligomeric assembly and exhibits amyloid-like attributes that could contribute for its pore-forming function. Biochemical Journal. 481 (22): 1679–1705.
Lata K, Anderluh G, Chattopadhyay K.* (2024) Entangling roles of cholesterol-dependent interaction and cholesterol-mediated lipid phase heterogeneity in regulating listeriolysin O pore-formation. Biochemical Journal. 481(19):1349-1377.
Verma P#, Chauhan A#, Thakur R, Lata K, Sharma A, Chattopadhyay K*, Mukhopadhaya A.* (2023) Vibrio parahaemolyticus thermostable direct haemolysin induces non-classical programmed cell death despite caspase activation. Molecular Microbiology. 120(6):845-873. doi: 10.1111/mmi.15180.[*Joint corresponding authors]
Bhutani G, Verma P, Jayachandran A, Paul S, Chattopadhyay K, De AK*. (2023) Unveiling the Role of Hidden Isomers in Large Stokes Shift in mKeima: Harnessing pH-Sensitive Dual-Emission in Bioimaging. J Phys Chem B. 127(14):3197-3207.
Kaur D#, Verma P#, Singh M, Sharma A, Lata K, Mukhopadhaya A*, Chattopadhyay K*. (2022) Pore formation-independent cell death induced by a b-barrel pore-forming toxin. FASEB Journal. 36(10):e22557. doi: 10.1096/fj.202200788R. [#Equal contribution][*Joint corresponding authors].
Mondal AK, Sengupta N, Singh M, Biswas R, Lata K, Lahiri I, Dutta S, Chattopadhyay K. (2022) Glu289 residue in the pore-forming motif of Vibrio cholerae cytolysin is important for efficient β-barrel pore formation. J Biol Chem. 298(10):102441. doi: 10.1016/j.jbc.2022.102441.
Mishra S, Kundu N, Pramanick I, Kumar A, Chattopadhyay K, Dutta S. (2023) Structural insights into thermostable direct hemolysin of Vibrio parahaemolyticus using single-particle cryo-EM. Proteins. 91(2):137-146.
Mondal, A. K., Lata, K., Singh, M., Chatterjee, S., Chauhan, A., Puravankara, S., Chattopadhyay, K. (2022) Cryo-EM elucidates mechanism of action of bacterial pore-forming toxins. Biochim Biophys Acta Biomembr. 1864(11):184013.
Gupta, T.#, Mondal, A. K.#, Pani, I., Chattopadhyay, K.*, Pal, S. K.* (2022) Elucidating liquid crystal-aqueous interface for the study of cholesterol-mediated action of a b-barrel pore forming toxin. Soft Matter. 18(28):5293-5301. [#Equal contribution first authors; *Joint corresponding authors]
Lata, K., Singh, M., Chatterjee, S., and Chattopadhyay, K. (2022) Membrane dynamics and remodelling in response to the action of the membrane-damaging pore-forming toxins. J. Membr. Biol. 255(2-3):161-173 .
Singh, M., Rupesh, N., Pandit, S. B., and Chattopadhyay K. (2022) Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin. Frontiers in Microbiology. 12:809782. doi: 10.3389/fmicb.2021.809782.
Mondal, A.K. and Chattopadhyay, K. (2022) Structures and functions of the membrane-damaging pore-forming proteins. Advances in Protein Chemistry and Structural Biology. 128:241-288.
Sengupta, N., Mondal, A. K., Mishra, S., Chattopadhyay, K., and Dutta, S.* (2021) Single particle Cryo-EM reveals conformational variability of the oligomeric VCC β-barrel pore in a lipid bilayer. Journal of Cell Biology. 220(12):e202102035. doi: 10.1083/jcb.202102035 [*Corresponding Author].
Verma, P. and Chattopadhyay, K. (2021) Current Perspective on the Membrane-Damaging Action of Thermostable Direct Hemolysin, an Atypical Bacterial Pore-forming Toxin. Frontiers in Molecular Biosciences. 23 July 2021 | https://doi.org/10.3389/fmolb.2021.717147.
Verma, P., Gandhi, S., Lata, K., Chattopadhyay, K. (2021) Pore-forming toxins in infection and immunity. Biochem. Soc. Trans. 49(1):455-465.
Mondal, A. K., Verma, P., Sengupta, N., Dutta, S., Pandit, S. B., and Chattopadhyay, K. (2021) Tyrosine in the hinge region of the pore-forming motif regulates oligomeric beta-barrel pore formation by Vibrio cholerae cytolysin. Molecular Microbiology. 115(4):508-525.
Mondal, A. K., Verma, P., Lata, K., Singh, M., Chatterjee, S., and Chattopadhyay, K. (2020) Sequence diversity in the pore-forming motifs of the membrane-damaging protein toxins. J. Membr. Biol. 253(5): 469-478.
Kundu, N., Verma, P., Kumar, A., Dhar, V., Dutta, S., and Chattopadhyay, K. (2020) N-terminal region of Vibrio parahaemolyticus thermostable direct hemolysin regulates the membrane-damaging action of the toxin. Biochemistry. 59(4): 605-614.
Mondal, A. K. and Chattopadhyay, K. (2020) Taking Toll on Membranes: Curious Cases of Bacterial β-Barrel Pore-Forming Toxins. Biochemistry. 59(2): 163-170. [This article is part of the Future of Biochemistry: The Asia-Pacific Issue special issue. ]
Mondal, A. K., Sreekumar, A., Kundu, N., Kathuria, R., Verma, P., Gandhi, S., and Chattopadhyay, K. (2018) Structural Basis and Functional Implications of the Membrane Pore-Formation Mechanisms of Bacterial Pore-Forming Toxins. Adv Exp Med Biol. 1112, 281-291 .
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.
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].
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.
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.
Khilwani, B., and Chattopadhyay, K. (2015) Signaling beyond punching holes: modulation of cellular responses by Vibrio cholerae cytolysin. Toxins, 7(8), 3344-3358.
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.
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.
Lata, K., and Chattopadhyay, K. (2015) Helicobacter pylori TlyA Forms Amyloid-like Aggregates with Potent Cytotoxic Activity. Biochemistry, 54 (23), 3649-3659.
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]
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.
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.
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.
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.
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.
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)
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.
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.

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