Microbial Interface Biology and associated host immune response
Key words: Streptococcus pneumoniae; Pathogenesis; Virulence factors; Mechanism of protection and immune evasion; Molecular Biology of B lymphocytes; Monoclonal antibodies
Summary of Research:
The theme of research is to decipher the molecular and cellular basis of immune response against protein and polysaccharide antigens present on the surface of the human bacterial pathogen Streptococcus pneumoniae (also called pneumococcus). The other area of research is to find out how pneumococcus causes disease and what interventions can be made to stop this from happening. The research is focused on the pneumococcal products and strategies that allow the pathogen to avoid being destroyed by the mammalian immune system, and the types of immune responses that can circumvent these products and strategies. The main objectives are (a) molecular analysis of immune response to pneumococcal cell surface protein and polysaccharide antigens, (b) identification and characterization of virulence factors such as toxins and adhesins from S. pneumoniae that are or may be related to pathogenesis, (c) how these virulence factors interact with the immune system and host cells to alter their cellular and molecular processes, and (d) evaluating the vaccine potential of pneumococcal cell surface proteins. We adopt a multidisciplinary approach to address these objectives. We combine molecular, genetic, immunological, microbiological and biochemical approaches with in vitro and in vivo models for these studies.
Sachin Kushwaha, Shabnam, Ankita Yadav, Pratiksha Shome, Jashobanta Behera, Rashi Jain, Rambodh Maurya and Chandradeep Roy
(1) Roy RP, Gupta K, Singh S, Khan N and Sehgal D (2021) A sortase-click reaction suite for defined protein dendrimer assembly: Synthetic example of a multivalent vaccine. Indian patent no. 358332.
(2) AnishCK, Khan N, Sehgal D and Panda AK (2020) Design and development of nanoparticles based carbohydrate vaccine against Streptococcus pneumoniae. Indian patent number 332055 granted on 14/02/2020.
(3) Sehgal D and Rohatgi S (2017) Ig genes specific oligonucleotides and uses thereof. European patent number 2100970 granted on 13/04/2017: Validated in United Kingdom.
(4) Sehgal D and Rohatgi S (2017) Ig genes specific oligonucleotides and uses thereof. Indian patent number 280165 granted on 13/02/2017.
(5) Sehgal D and Rohtagi S (2012) Nested primer sets for amplifying mouse immunoglobulin variable gene segments. US patent number 8143007 granted on 27/03/2012.
- Parray HA, Narayanan N, Garg S, Rizvi ZA, Shrivastava T, Kushwaha S, Singh J, Murugavelu P, Anantharaj A, Mehdi F, Raj N, Singh S, Dandotiya J, Lukose A, Jamwal D, Kumar S, Chiranjivi AK, Dhyani S, Mishra N, Kumar S, Jakhar K, Sonar S, Panchal AK, Tripathy MR, Chowdhury SR, Ahmed S, Samal S, Mani S, Bhattacharyya S, Das S, Sinha S, Luthra K, Batra G, Sehgal D, Medigeshi GR, Sharma C, Awasthi A, Garg PK, Nair DT and Kumar R. (2022) A broadly neutralizing monoclonal antibody overcomes the mutational landscape of emerging SARS-CoV-2 variants of concern. PLoS Pathog. 18(12):e1010994.
- Ahuja R, Shelly A, Meena J, Singh M, Sehgal D and Panda AK (2022) Enhanced immunogenicity of recombinant pneumococcal protein delivered using thermostable polymer particles. Mater Today Commun. 32: 103894.
- Singh M, Sori H, Ahuja R, Meena J, Sehgal D and Panda AK (2020) Effect of N-terminal poly histidine-tag on immunogenicity of Streptococcus pneumoniae surface protein SP0845. Int J BiolMacromol., 163: 1240-1248.
- Kaushal N, Kumari S, Jhelum H and Sehgal D (2020) In vitro and in vivo characterization of the interaction, proinflammatory, immunomodulatory and antigenic properties of capsular polysaccharide from Streptococcus pneumoniae serotype 1. Int J BiolMacromol., 143: 521-532.
- Jha B, Vyas R, Bhushan J, Sehgal D and Biswal BK (2019) Structural insights into substrate specificity of SP_0149, the substrate binding protein of a methionine ABC transporter from Streptococcus pneumoniae. Acta Crystallogr Sect F Struct Biol Cryst Commun 75: 520-528.
- Jhelum H, Sori H and Sehgal D (2018) A novel extracellular vesicle-associated endodeoxyribonuclease helps Streptococcus pneumoniae evade neutrophil extracellular traps and is required for full virulence. Sci Rep 8:7985.
- Vashishta M, Khan N, Mehto S, Sehgal D and Natarajan K (2015) Pneumococcal surface protein A (PspA) regulates Programmed death ligand 1 expression on dendritic cells in a Toll-like receptor 2 and calcium dependent manner. PLoS One 10: e0133601.
- Saxena S, Khan N, Dehinwal R, Kumar A and Sehgal D (2015) Conserved surface accessible nucleoside ABC transporter component SP0845 is essential for pneumococcal virulence and confers protection in vivo. PLoS One 10: e0118154.
- Khan N, Qadri RA and Sehgal D (2015) Correlation between in vitro complement deposition and passive mouse protection of anti-Pneumococcal surface protein A monoclonal antibodies. Clin Vaccine Immunol 22: 99-107.
- Rohatgi S, Ganju P and Sehgal D (2008) Systematic design and testing of nested (RT-)PCR primers for specific amplification of mouse rearranged/expressed immunoglobulin variable region genes from small number of B cells. J Immunol Methods 339: 205-19.
- Kaushik DK and Sehgal D (2008) Developing vaccines against bacterial pathogens in genomics and proteomics era. Scand J Immunol 67: 544-52.
- Anish C, Upadhyay AK, Sehgal D and Panda AK (2014) Influences of process and formulation parameters on powder flow properties and immunogenicity of spray dried polymer particles entrapping recombinant pneumococcal surface protein A. Int J Pharm 466: 198-210.
- Anish C, Khan N, Upadhyay AK, Sehgal D and Panda AK (2014) Delivery of polysaccharides using polymer particles: implications on size-dependent immunogenicity, opsonophagocytosis, and protective immunity. Mol Pharm 11: 922-37.
- Gupta K, Singh S, Gupta K, Khan N, Sehgal D, Haridas V and Roy RP (2012) A bioorthogonal chemoenzymatic strategy for defined protein dendrimer assembly. Chembiochem 13: 2489-94.
- Misra A, Biswas T, Das S, Marathe U, Sehgal D, Roy RP and Ramakumar S (2011) Crystallization and preliminary X-ray diffraction studies of Sortase A from Streptococcus pneumoniae. Acta Crystallogr Sect F Struct Biol Cryst Commun 67: 1195-98.
- Bhushan J, Vyas R, Sharma T, Sehgal D and Biswal BK (2011) Cloning, overexpression, purification, crystallization, and preliminary X-ray studies of SP_0149, the substrate binding protein of an ABC transporter from Streptococcus pneumoniae. Acta Crystallogr Sect F Struct Biol Cryst Commun 67: 797-99.
- Madhavi Y, Puliyel JM, Mathew JL, Raghuram N, Phadke A, Shiva M, Srinivasan S, Paul Y, Srivastava RN, Parthasarathy A, Gupta S, Ranga U, Lakshmi VV, Joshi N, Nath I, Gulhati CM, Chatterjee P, Jain A, Priya R, Dasgupta R, Sridhar S, Dabade G, Gopakumar KM, Abrol D, Santhosh MR, Srivastava S, Visalakshi S, Bhargava A, Sarojini NB, Sehgal D, Selvaraj S and Banerji D. (2010) Evidence-based national vaccine policy. Indian J Med Res 131: 617-28.
- Rohatgi S, Dutta D, Tahir S and Sehgal D (2009) Molecular dissection of antibody responses against Pneumococcal surface protein A: Evidence for diverse ‘DH-less’ heavy chain gene usage and avidity maturation. J Immunol 182: 5570-85.