Structural biology of host-microbe interactions in health and disease, bacterial pili and biofilm

Many bacteria assemble multitude of surface proteins and assemblies like pili to adhere to biotic and abiotic surfaces. This bacterial adherence is a key step for bacterial colonization, pathogenesis, and even for beneficial effects to the host and environment. The structural biology of Gram-positive bacterial pili is an emerging area of research, while much progress has been made in Gram-negative bacterial pili. Pili of Gram-negative bacteria are composed of non-covalently assembled protein subunits (pilins), for example, chaperon/usher assembled pili, type IV pili, curli pili. In contrast, the pili in Gram-positive bacteria are made of covalently linked pilins with the help of cysteine proteases called sortases. The presence of pilus gene clusters that encode pilins and related proteins have been identified in several Gram-positive organisms. Certain unique structural features possibly dictate the diversity in their cellular targets and the resulting infections or beneficial effects distinguish these organisms and their pilus type from one another. Our lab works on bacterial cell surface adhesins with focus on pilus-like structures in Gram-positive pathogenic and non-pathogenic organisms towards understanding their architecture and assembly, and their role in adherence and biofilm formation.

• Priyanka Chauraisa
  Senior Research Fellow
  [email protected]
• Abhiruchi Kant
  Senior Research Fellow
  [email protected]
• Abhin Kumar Megta
  Senior Research Fellow
  [email protected]
• Rajnesh Kumari Yadav
  Senior Research Fellow
  [email protected]
• Shivendra Pratap
  Young Investigator
  [email protected]
• Smita Yadav
  Junior Research Fellow
  [email protected]
• Amar Prajapati
  Junior Research Fellow
  [email protected]

1. Chaurasia P, Pratap S, , Palva A, von Ossowski I, Krishnan V. (2018) Bent conformation of a backbone pilin N-terminal domain supports a three-stage pilus assembly mechanism. Commun Biol 1:94
2. Mishra AK, Megta AK, Palva A, von Ossowski I, Krishnan V. (2017) Crystallization and X-ray diffraction analysis of SpaE, a basal pilus protein from the gut-adapted Lactobacillus rhamnosus GG. Acta Crystallogr F Struct Biol Commun 73:321
3. Krishnan V, Kant A, Chaurasia P (2016) Pili in Probiotic Bacteria in “Prebiotics and Probiotics in Human Nutrition and Health", ISBN 978-953-51-4715-2, InTech:115
4. Chaurasia P, Pratap S, von Ossowski I, Palva A, Krishnan V, (2016) New insights about pilus formation in gut-adapted Lactobacillus rhamnosus GG from the crystal structure of the SpaA backbone-pilin subunit. Sci Rep. 6:28664
5. Kant A, von Ossowski I, Palva A, Krishnan V (2016)  Crystallization and X-ray Crystallographic Analysis of the Adhesive SpaC Pilin Subunit in the SpaCBA Pilus of Gut-adapted Lactobacillus rhamnosus GG. Protein & Peptide Letters 23:365
6. Chaurasia P, von Ossowski I, Palva A, Krishnan V. (2015) X-ray diffraction analysis of two crystals forms of backbone pilin SpaA fragment from Lactobacillus rhamnosus GG. Journal of proteins and proteomics 6:30
7. Krishnan V (2015)  Pilins in gram-positive bacteria: A structural perspective. IUBMB Life 67:533
8. Chaurasia P, von Ossowski I, Palva A, Krishnan V, (2015) Purification, crystallization and preliminary X-ray diffraction analysis of SpaD, a backbone-pilin subunit encoded by the fimbrial spaFED operon in Lactobacillus rhamnosus GG. Acta Crystallogr F71:103.
9. Chen C, Vengadesan K, Macon K, Manne K, Narayana SV, Schneewind O. (2013) Secreted Proteases Control Autolysin-mediated Biofilm Growth of Staphylococcus aureus. Journal of Biological Chemistry 288:29440.
10. Singh D, von Ossowski I, Palva A, Vengadesan k.(2013) Purification, crystallization and preliminary crystallographic analysis of the SpaA backbone-pilin subunit from probiotic Lactobacillus rhamnosus GG. Acta Crystallogr Sect F Struct Biol Cryst Commun 69:1182.
11. Vengadesan K, Dwivedi P, Kim BJ, Samal A, Macon K, Ma X, Mishra A, Doran KS, Ton-That H, Narayana SV.(2013) Structure of Streptococcus agalactiae tip pilin GBS104: a model for GBS pili assembly and host interactions. Acta Crystallographica Section D: Biological Crystallography 69:1073.
12. Vengadesan K, Macon K, Sugumoto S, Mizunoe Y, Iwase T, Narayana SV.(2013) Purification, crystallization and preliminary X-ray diffraction analysis of the Staphylococcus epidermidis extracellular serine protease Esp. Acta Crystallogr Sect F Struct Biol Cryst Commun 69(Pt1):49.
13. Vengadesan, K. and S. V. L. Narayana. (2011) Structural biology of gram-positive bacterial adhesins. Protein Science 20(5):759.
14. Vengadesan K, Ma X, Dwivedi P, Ton-That H, Narayana SV. (2011) A Model for Group B Streptococcus Pilus Type 1: The Structure of a 35-kDa C-Terminal Fragment of the Major Pilin GBS80. Journal of molecular biology 407(5):731.
15. Mishra A, Devarajan B, Reardon ME, Dwivedi P, Krishnan V, Cisar JO, Das A, Narayana SV, Ton-That H.(2011) Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development. Molecular microbiology 81(5):1205.
16. Vengadesan K, Macon K, Sugumoto S, Mizunoe Y, Iwase T, Narayana SV.(2011) Crystallography of gram-positive bacterial adhesins. Adv Exp Med Biol 715: 175.
17. Khare B, Vengadesan K, Rajashankar KR, I-Hsiu H, Xin M, Ton-That H, Narayana SV. (2011) Structural Differences between the Streptococcus agalactiae Housekeeping and Pilus-Specific Sortases: SrtA and SrtC1. PLoS One 6(8):e22995.
18. Vengadesan K, Ma X, Dwivedi P, Ton-That H, Narayana SV. (2010) Purification, crystallization and halide phasing of a Streptococcus agalactiae backbone pilin GBS80 fragment. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 66(12):1666.
19. Khare B, Samal A, Vengadesan K, Rajashankar KR, Ma X, Huang IH, Ton-That H, Narayana SV. (2010) Preliminary crystallographic study of the Streptococcus agalactiae sortases, sortase A and sortase C1. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 66(9):1096.
20. Vengadesan K, Xu Y, Macon K, Volanakis JE, Narayana SV. (2009) The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. Acta Crystallographica Section D: Biological Crystallography 65(3):266.
21. Vengadesan K, Ponnuraj K, Xu Y, Macon K, Volanakis JE, Narayana SV.(2009) The crystal structure of cobra venom factor, a cofactor for C3-and C5-convertase CVFBb. Structure 17(4):611.
22. Vengadesan K, Macon K, Narayana SV. (2008) The crystal structure of cobra venom factor, a complement-activating protein from Naje Naja Kouthia. Molecular Immunology 45(16):4120.
23. Vengadesan K, XU Y, Macon K, Volanakis JE, Narayana SV. (2007) The Crystal Structure of C2a, the Catalytic Fragment of Classical Pathway C3-and C5-convertase of Human Complement. Journal of molecular biology 367(1):224.
24. Vengadesan K, XU Y,Macon K, Narayana SV. (2007) Crystal structure of C2a, the catalytic subunit of classical pathway C3-convertase. Molecular Immunology 44(1):199.
25. Vengadesan K, Gaspar AH, Ye N, Mandlik A, Ton-That H, Narayana SV. (2007) An IgG-like Domain in the Minor Pilin GBS52 of Streptococcus agalactiae Mediates Lung Epithelial Cell Adhesion. Structure 15(8):893.
26. Gautham N, Vengadesan K. (2003) METHOD AND SYSTEM TO BUILD OPTIMAL MODELS OF 3-DIMENSIONAL MOLECULAR STRUCTURES, US Patent.
27. Vengadesan K, Gautham N. (2005) A new conformational search technique and its applications. Curr Sci 88:1759.
28. Prasad PA, Vengadesan K, Gautham N. (2005) MOLS-A program to explore the potential energy surface of a peptide and locate its low energy conformations. In silico biology 5(4):401.
29. Vengadesan K, Gautham N. (2004) Conformational studies on enkephalins using the MOLS technique. Biopolymers 74(6):476.
30. Vengadesan K, Gautham N. (2004) Energy landscape of Met-enkephalin and Leu-enkephalin drawn using mutually orthogonal Latin squares sampling. The Journal of Physical Chemistry B 108(30):11196.
31. Vengadesan K, Anbupalam T, Gautham N. (2004) An application of experimental design using mutually orthogonal Latin squares in conformational studies of peptides. Biochem Biophys Res Commun 316(3):731.
32. Vengadesan K, Gautham N. (2003) Enhanced sampling of the molecular potential energy surface using mutually orthogonal Latin squares: Application to peptide structures. Biophysical journal 84(5):2897.
33. Gautham N, Vengadesan K. (2003) METHOD AND SYSTEM TO BUILD OPTIMAL MODELS OF 3-DIMENSIONAL MOLECULAR STRUCTURES, WO Patent 081:510.
34. Thirumurugan R, Vengadesan K, Raj SS, Shanmugam G, Fun HK. (2000) Crystal Structure of N, N'-Bis (3-(o-dimethylaminoimino-ethyl)-2-hydroxy-5-methyl)-benzylpiperazine. Crystal Research and Technology 35(8):987.