Saumen Datta , Ph.D.

Chief Scientist
Structural Biology & Bioinformatics
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Research Interest

Exploring Bacterial Virulence Determinants: Comprehensive High-Resolution Structural Studies for Uncovering Novel Therapeutic Targets from Pathogenic Bacteria like Pseudomonas aeruginosa, Yersinia spp. And vibrio spp.

Our laboratory is dedicated to researching the fascinating world of microbial warfare, where bacteria engage in intricate battles for survival and dominance. We focus on understanding the three key players in this microbial arms race: the Type III Secretion System (T3SS), the Type VI Secretion System (T6SS), and Quorum Sensing. The complex interplay of these systems underscores their significant impact on bacterial virulence and communication. T3SS and T6SS allow bacteria to inject toxins directly into host cells or neighboring microbes, thus promoting pathogenesis and interbacterial competition. Meanwhile, quorum sensing coordinates behaviors within bacterial populations, regulating crucial processes such as virulence factor production and biofilm formation. By targeting these systems, we can develop promising therapeutic interventions that impede bacterial pathogenicity and community dynamics. Understanding the mechanisms underlying T3SS, T6SS, and quorum sensing is key to developing novel strategies to combat infectious diseases, enhance antibiotic efficacy, and manipulate microbial communities for beneficial outcomes.

The type three secretion system (T3SS) is a major virulence determining factor in numerous plants and animal pathogenic bacteria. A broad spectrum of diseases is caused by pathogenic bacteria, such as enteric infections caused by enteropathogenic E. coli, Shigella, Salmonella, and Y. enterocolitica containing T3SS. Pseudomonas aeruginosa is one of the six antimicrobial-resistant nosocomial “ESKAPE” pathogens of high priority, enlisted by the World Health Organization, which increases the burden of disease globally due to its intrinsic, acquired and adaptive resistance to different antibiotics and drugs conferred by its genome plasticity and adaptability. These pathogens use T3SS to inject effector toxins directly inside the host cell to manipulate host cellular processes. Mutations, deletions, or blocking of the T3SS apparatus components result in reduced virulence and disease manifestations in mouse model experiments. T3SS has been predicted to evolve from flagellar T3SS (fT3SS) through horizontal gene transfer, and both share a common ancestor. Both T3SS and fT3SS share many structurally similar components at their core. Bacterial T3SS is a complex structure composed of approximately 20 different proteins and broadly can be divided into three basic parts, namely the basal body, needle complex, and a large cytosolic component known as the sorting platform or the C-ring complex. The basal body consists of two co-axial homomeric protein complex rings across the inner and outer plasma membrane, including the peptidoglycan layer. The needle is associated with the outer ring projecting away from the bacterial membrane, providing approximately 1.5–2.5 nm conduit to translocate unfolded effectors. Tip complex protein associated with the needle helps the bacteria to integrate with the host plasma membrane. Once the association with the host membrane is established, the export apparatus helps translocate effectors through the needle to the host cell cytoplasm. Previous structural studies involving Cryo-Electron microscopy have revealed the global structure of the T3SS Injectisome. However, the precise details of the cytoplasmic components are largely undetermined because of their dynamic nature of association with the injectisome.

In this backdrop, we want to solve the atomic resolution structure of T3SS injectisome associated ATPase and ATPase complex with other C-ring proteins from Pseudomonas aeruginosa and Yersinia enterocolitica by X-ray diffraction or Cryo-EM methods. Another essential part of the injectisome is the translocon, which makes a pore in the host cell. We will make various translocatory proteins and reconstitute the translocation complex, known as translocon, in vitro and decipher the structures of different translocatory proteins and the translocon.

 

The effectors produced by Pseudomonas aeruginosa and Yersinia spp. are highly versatile and perform various functions within the host cell to manipulate its functions to the advantage of the bacteria for their survival and spread. Our laboratory aims to uncover the different roles of these effectors within the host cells by identifying their corresponding partners in the host cell and determining the atomic resolution structures of these complexes.

Credentials

  • Senior Research Fellow, University of Limerick, Ireland 2008
  • Quick Hire Fellow, CSIR-CLRI, Chennai, India, 2004-2006
  • Assistant Research Scientist, John Hopkins University, Maryland, USA 2002-2004
  • Postdoctoral Associate, Washington University in St. Louis, Missouri, USA, 1999-2002
  • Postdoctoral Associate, University of Connecticut, USA, 1998-1999
  • Ph.D, IISc, Bangalore, Indian

Patents & Publications

  1. G Basu Choudhury, S Datta*. Implication of Molecular Constraints Facilitating the Functional Evolution of Pseudomonas aeruginosa KPR2 into a Versatile α-Keto-Acid Reductase. Biochemistry. 2024 Jul 4. doi: 10.1021/acs.biochem.4c00087. Online ahead of print.
  2. Pramanik A, Datta S*. Structural and functional insights of itaconyl-CoA hydratase from Pseudomonas aeruginosa highlight a novel N-terminal hotdog fold. FEBS Lett doi: 10.1002/1873-3468.14867.
  3. Choudhury A, Saha S, Maiti NC, Datta S*. Exploring structural features and potential lipid interactions of Pseudomonas aeruginosa type three secretion effector PemB by spectroscopic and calorimetric experiments. Protein Sci. 2023 Apr;32(4):e4627. doi: 10.1002/pro.4627.PMID: 36916835
  4. Sen H, Choudhury GB, Pawar G, Sharma Y, Bhalerao SE, Chaudhari VD, Datta S*, Raychaudhuri S. Diversity in the ligand binding pocket of HapR attributes to its uniqueness towards several inhibitors with respect to other homologues - A structural and molecular perspective. Int J Biol Macromol. 2023 Feb 2;233:123495. doi: 10.1016/j.ijbiomac.2023.123495.
  5. Kumar R, Roy C, S. Datta*. Delineating specific regions of N- terminal domain of T3SS ATPase YsaN of Yersinia enterocolitica governing its different oligomerization states. Front Mol Biosci. 2022 Sep 8;9:967974. doi: 10.3389/fmolb.2022.967974.
  6. Choudhury A, Khanppnavar B, Datta S*. Crystallographic and biophysical analyses of Pseudomonas aeruginosa ketopantoate reductase: Implications of ligand induced conformational changes in cofactor recognition. Biochimie. 2022 Feb;193:103-114. doi: 10.1016/j.biochi.2021.10.015.
  7. Roy C, Kumar R, Hossain MM, Das A, Datta S*. Biophysical and Computational Approaches to Unravel pH-Dependent Conformational Change of PspA Assist PspA-PspF Complex Formation in Yersinia enterocolitica. Protein J. 2022 Jun;41(3):403-413. doi: 10.1007/s10930- 022-10061-w. Epub 2022 Jun 16. PMID: 35708879.
  8. Ekka M, Mondal A, Singh R, Sen H, Datta S, Raychaudhuri S. Arginine 37 of Glycine Linker Dictates Regulatory Function of HapR. Front Microbiol. 2020 Aug 21;11:1949. doi: 10.3389/fmicb.2020.01949.
  9. Roy C, Kumar R, Datta S*. Comparative Studies on Ion-pair Energetic, Distribution among Three Domains of Life: Archaea, Eubacteria and Eukarya. Proteins. 2020 Jan 30. doi: 10.1002/prot.25878. [Epub ahead of print] PubMed PMID: 31999377.
  10. Khanppnavar B, Chatterjee R, Choudhury GB, Datta S*. Genome-wide survey and crystallographic analysis suggests a role for both horizontal gene transfer and duplication in pantothenate biosynthesis pathways. Biochim Biophys Acta Gen Subj. 2019 Oct;1863(10):1547-1559. doi: 10.1016/j.bbagen.2019.05.017. Epub 2019 May 25. PubMed PMID: 31136784.
  11. Halder PK, Roy C, Datta S*. Structural and functional characterization of type three secretion system ATPase PscN and its regulator PscL from Pseudomonas aeruginosa. Proteins. 2019 Apr;87(4):276-288. doi: 10.1002/prot.25648. Epub 2018 Dec 30. PubMed PMID: 30561072.
  12. Roy C, Datta S*. ASBAAC: Automated Salt-Bridge and Aromatic-Aromatic Calculator. Bioinformation. 2018 Apr 30;14(4):164-166. doi: 10.6026/97320630014164. eCollection 2018. PubMed PMID: 29983486; PubMed Central PMCID: PMC6016756.
  13. Khanappnavar B, Datta S*. Crystal structure and substrate specificity of ExoY, a unique T3SS mediated secreted nucleotidyl cyclase toxin from Pseudomonas aeruginosa. Biochim Biophys Acta. 2018 Sep;1862(9):2090-2103
  14. Mondal A, Chatterjee R, Datta S*. Umbrella Sampling and X-ray Crystallographic Analysis Unveil an Arg-Asp Gate Facilitating Inhibitor Binding Inside Phosphopantetheine Adenylyltransferase Allosteric Cleft. J Phys Chem B. 2018 Feb 8;122(5):1551-1559.
  15. Mondal A, Datta S*. Quantum mechanical electronic structure calculation reveals orientation dependence of hydrogen bond energy in proteins. Proteins. 2017 Jun;85(6):1046-1055.
  16. Chatterjee R, Mondal A, Basu A, Datta S*. Transition of phosphopantetheineadenylyltransferase from catalytic to allosteric state is characterized by ternary complex formation in Pseudomonas aeruginosa. Biochim Biophys Acta. 2016 Jul;1864(7):773-86.
  17. Basu A, Das A, Mondal A, Datta S*. Structural analysis of inter-genus complexes of V-antigen and its regulator and their stabilization by divalent metal ions. Eur Biophys J. 2016 Mar;45(2):113-28.
  18. Basu A, Das U, Dey S, Datta S*. PcrG protects the two long helical oligomerization domains of PcrV, by an interaction mediated by the intramolecular coiled-coil region of PcrG. BMC Struct Biol. 2014 Jan 24;14(1):5.
  19. Dey S, Datta S*. Interfacial residues of SpcS chaperone affects binding of effector toxin ExoT in Pseudomonas aeruginosa: novel insights from structural and computational studies. FEBS. J. 2014 Jan 4
  20. Chatterjee R, Halder PK, Datta S*. Identification and molecular characterization of YsaL (Ye3555): a novel negative regulator of YsaN ATPase in type three secretion system of enteropathogenic bacteria Yersinia enterocolitica. PLoS One. 2013 Oct 4;8(10):e75028.
  21. Basu A, Chatterjee R, Datta S*. YspC: a unique translocator exhibits structural alteration in the complex form with chaperone SycB. Protein J. 2012 Aug;31(6):487-98.
  22. Dey S, Basu A, Datta S*. Characterization of molten globule PopB in absence and presence of its chaperone PcrH. Protein J. 2012 Jun;31(5):401-16.
  23. Basu A, Chatterjee R, Datta S*. Expression, Purification, Structural and Functional Analysis of SycB: A Type Three Secretion Chaperone From Yersinia enterocolitica. Protein J. 2012 Jan;31(1):93-107.
  24. Chen ZW, Datta S, Dubois JL, Klinman JP, Mathews FS. Mutation at a strictly conserved, active site tyrosine in the copper amine oxidase leads to uncontrolled oxygenase activity. Biochemistry. 2010 Aug 31;49(34):7393-402.
  25. Larkin C, Datta S, Harley MJ, Anderson BJ, Ebie A, Hargreaves V, Schildbach JF. Inter- and intramolecular determinants of the specificity of single-stranded DNA binding and cleavage by the F factor relaxase. Structure. 2005 Oct;13(10):1533-44.
  26. Aravinda S, Datta S, Shamala N, Balaram P. Hydrogen-bond lengths in polypeptide helices: no evidence for short hydrogen bonds. Angew Chem Int Ed Engl. 2004 Dec 10;43(48):6728- 31.
  27. Datta S, Rathore RN, Vijayalakshmi S, Vasudev PG, Rao RB, Balaram P, Shamala N. Peptide helices with pendant cycloalkane rings. Characterization of conformations of 1- aminocyclooctane-1-carboxylic acid (Ac8c) residues in peptides. J Pept Sci. 2004 Mar;10(3):160-72.
  28. Datta S, Larkin C, Schildbach JF. Structural insights into single-stranded DNA binding and cleavage by F factor TraI. Structure. 2003 Nov;11(11):1369-79.
  29. Datta S, Ikeda T, Kano K, Mathews FS. Structure of the phenylhydrazine adduct of the quinohemoprotein amine dehydrogenase from Paracoccus denitrificans at 1.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2003 Sep;59(Pt 9):1551-6.
  30. Larkin C, Datta S, Nezami A, Dohm JA, Schildbach JF. Crystallization and preliminary X-ray characterization of the relaxase domain of F factor TraI. Acta Crystallogr D Biol Crystallogr. 2003 Aug;59(Pt 8):1514-6.
  31. Datta S, Mori Y, Takagi K, Kawaguchi K, Chen ZW, Okajima T, Kuroda S, Ikeda T, Kano K, Tanizawa K, Mathews FS. Structure of a quinohemoprotein amine dehydrogenase with an uncommon redox cofactor and highly unusual crosslinking. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14268-73.
  32. Datta S, Uma MV, Shamala N, Balaram P. Stereochemistry of Schellman Motifs in Peptides. Crystal Structure of a Hexapeptide with a C-terminus 6 1 Hydrogen Bond. Biopolymers 1999 50; 13-22
  33. Datta S, Shamala N, Banerjee A, Balaram P. Hydrogen bonding in peptide helices. Analysis of two independent helices in the crystal structure of a peptide Boc-Val-Ala-Leu-Aib-Val-Ala- PheOMe. J Pept Res. 1997 Jun;49(6):604-11.
  34. Datta S, Shamala N, Banerjee A, Balaram P. Conformational Variability of Gly-Gly Segments in Peptides. A Comparison of the Crystal Structures of an Acyclic Pentapeptide and an Octapeptide. Bioplolymers 1997: 41; 331-336.
  35. Datta S, Kaul R, Rao RB, Shamala N, Balaram P. Stereochemistry of Linking Segments in the Design of Helix-Helix Motifs in Peptides: Crystallographic Comparison of a Glycyl- DipropylGlycyl Segment in a Tripeptide and in a 14 residue peptide. J. Chem. Soc., Perkin Trans. 1997:2; 1659-1664.
  36. Datta S, Shamala N, Banerjee A, Pramanik A, Bhattacharya S, Balaram P. Characterization of Helix Terminating Schellman Motifs in Peptides. Crystal Structure and Nuclear Overhausser Effect Analysis of a Synthetic Heptapeptide Helix. J. Am. Chem. Soc. 1997, 119; 9246-9251.
  37. Banerjee A, Datta S, Pramanik A, Shamala N, Balaram P. Heterogeneity and Stability of Helical Conformation in Peptides: Crystallographic and NMR studies of a Model Heptapeptide. J. Am. Chem. Soc. 1996, 118; 9477-9483.
  38. Datta S, Shamala N, Gurunath R, Balaram P. Observation of a mixed antiparallel and parallel beta-sheet motif in the crystal structure of Boc-Ala-Ile-Aib-OMe. Int J Pept Protein Res. 1996, Sep;48(3):209-14.
  39. S. Datta, K. Kano, T. Ikeda, K. Tanizawa, and F. S. Mathews. Crystal structure of an inactive, precursor form of quinohemoprotein amine dehydrogenase from Paracoccus denitrificans.
  40. S. Datta, S. A. White, P. Tricky and F. S. Mathews. Crystal structure of the complex flavoenzyme trimethylamine dehydrogenase from Methylophilus methylotrophus W3A1 at 0.94 Å resolution.
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