Abstract
Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surrounding the brain and spinal cord, is a major cause of death and disability all over the world. From perinatal period to adult, four common organisms responsible for most of the bacterial meningitis are Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenza and Staphylococcus aureus. As the disease is caused by more organisms, currently available vaccines for bacterial meningitis are specific and restricted to some of the serogroups or serotypes of each bacterium. In an effort to design common vaccine against bacterial meningitis, proteomes of the four pathogens were compared to extract seven common surface exposed ABC transporter proteins. Pro-Pred server was used to investigate the seven surface exposed proteins for promiscuous T-cell epitopes prediction. Predicted 22 T-cell epitopes were validated through published positive control, SYFPEITHI and immune epitope database to reduce the epitope dataset into seven. T-cell epitope 162-FMILPIFNV-170 of spermidine/putrescine ABC transporter permease (potH) protein was conserved across the four selected pathogens of bacterial meningitis. Hence, structural analysis was extended for epitope 162-FMILPIFNV-170. Crystal structures of HLA-DRB alleles were retrieved and structure of potH was modeled using Prime v3.0 for structural analysis. Computational docking of HLA-DRB alleles and epitope 162-FMILPIFNV-170 of potH was performed using Glide v5.7. RMSD and RMSF of simulation studies were analyzed by Desmond v3.2. The docking and simulation results revealed that the HLA-DRB-epitope complex was stable with interaction repressive function of HLA. Thus, the epitope would be ideal candidate for T-cell driven subunit vaccine design against bacterial meningitis.
References
Altschul, S.F., Thomas, L.M., Alejandro, A.S., Jinghui, Z., Zheng, Z., Webb, M., David J.L. 1997. Gapped BLAST and PSI BLAST: A new generation of protein database search programs. Nucl Acid Res 25, 3389–3402.
Bandaru, N.R., Ibrahim, M.K., Nuri, M.S., Suliman, M.E. 1998. Etiology and occurrence of acute meningitis in children Benghazi, Libyan Arab Jamahiriya. East Mediterr Health J 4, 50–57.
Barker, C.J., Beagley, K.W., Hafner, L.M., Timms, P. 2008. In silico identification and in vivo analysis of a novel T-cell antigen from Chlamydia, NrdB. Vaccine 26, 1285–1296.
Bharathi, M.J., Ramakrishnan, R., Vasu, S., Meenakshi, R., Shivkumar, C.R., Palaniappan, R. 2003. Epidemiology of bacterial keratitis in a referral centre in south india. Indian J Med Microbiol 21, 239–245.
Brooks, W., Daniel, K., Sung, S., Guida, W. 2008. Computational validation of the importance of absolute stereochemistry in virtual screening. J Chem Inf Model 48, 639–645.
Choudhuri, S. 2006. Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters. Int J of Toxicol 25, 231–259.
Dass, J.F.P., Deepika, V. 2008. Implications from predictions of HLA-DRB1 binding peptides in the membrane proteins of Corynebacterium diphtheriae. Bioinformation 3, 111–113.
Doolan, D.L., Southwood, S., Chesnut, R., Appella, E., Gomez, E., Richards, A., Higashimoto, Y.I., Maewal, A., Sidney, J., Gramzinski, R.A., Mason, C., Koech, D., Hoffman, S.L., Sette, A. 2000. HLA-DRpromiscuous T cell epitopes from Plasmodium falciparum preerythrocytic — stage antigens restricted by multiple HLA class II alleles. J Immunol 165, 1123–1137.
Essmann, U., Perera, L., Berkowitz, M.L., Darden, T., Lee, H., Pedersen, L.G. 1995. A smooth particle mesh Ewald method. J Chem Phys 103, 8577–8593.
Friesner, R.A., Banks, J.L., Murphy, R.B., Halgren, T.A., Klicic, J.J., Mainz, D.T., Repasky, M.P., Knoll, E.H., Shelley, M., Perry, J.K., Shaw, D.E., Francis, P., Shenkin, P.S. 2004. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47, 1739–1749.
Friesner, R.A., Murphy, R.B., Repasky, M.P., Frye, L.L., Greenwood, J.R., Halgren, T.A., Sanschagrin, P.C., Mainz, D.T. 2006. Extra precision glide docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49, 6177–6196.
Ginsberg, L. 2004. Difficult and recurrent meningitis. J Neurol Neurosurg Psychiatry 75, 16–21.
Halgren, T.A., Murphy, R.B., Friesner, R.A., Beard, H.S., Frye, L.L., Pollard, W.T., Banks, J.L. 2004. Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47, 1750–1759.
Huang, S.H., Jong, A.Y. 2001. Cellular mechanisms of microbial proteins contributing to invasion of the blood-brain barrier. Cell Microbiol 3, 277–287.
Jorgensen, W.L., Maxwell, D.S., TiradoRives, J. 1996. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118, 11225–11236.
Kaminski, G.A., Friesner, R.A., Tirado-Rives, J., Jorgensen, W.L. 2001. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J Phys Chem B 105, 6474–6487.
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M. 1993. PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Cryst 26, 283–291.
Locher, K.P., Lee, A.T., Rees, D.C. 2002. The E. coli BtuCD structure: A framework for ABC transporter architecture and mechanism. Science 296, 1091–1098.
Maestro v9.2, 2011. Schrödinger, LLC, New York.
Mani, R., Pradhan, S., Nagarathna, S., Wasiulla, R., Chandramuki, A. 2007. Bacteriological profile of community acquired acute bacterial meningitis: A ten-year retrospective study in a tertiary neurocare centre in South India. Indian J Med Microbiol 25, 108–114.
Mora, M., Bensi, G., Capo, S., Falugi, F., Zingaretti, C., Manetti, A.G., Maggi, T., Taddei, A.R., Grandi, G., Telford, J.L. 2005. Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens. Proc Natl Acad Sci 102, 15641–15646.
Mustafa, A.S., Shaban, F.A. 2006. ProPred analysis and experimental evaluation of promiscuous T-cell epitopes of three major secreted antigens of Mycobacterium tuberculosis. Tuberculosis 86, 115–124.
Mwangi, M.M., Wu, S.W., Zhou, Y., Sieradzki, K., de Lencastre, H., Richardson, P., Bruce, D., Rubin, E., Myers, E., Siggia, E.D., Tomasz, A. 2007. Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing. Proc Natl Acad Sci 104, 9451–9456.
Oftung, F., Lundin, K.E.A., Geluk, A., Shinnick, T.M., Meloen, R., Mustafa, A.S. 1997. Primary structure and MHC restriction of peptide defined T cell epitopes from recombinantly expressed mycobacterial protein antigens. Med Princples Pract 6, 66–73.
Panigada, M., Sturniolo, T., Besozzi, G., Boccieri, M.G., Sinigaglia, F., Grassi, G.G., Grassi, F. 2002. Identification of a promiscuous T-cell epitope in Mycobacterium tuberculosis Mce proteins. Infect Immun 70, 79–85.
Peters, B., Sette, A. 2007. Integrating epitope data into the emerging web of biomedical knowledge resources. Nat Rev Immunol 7, 485–490.
Peters, B., Sidney, J., Bourne, P., Bui, H.H., Buus, S., Doh, G., Fleri, W., Kronenberg, M., Kubo, R., Lund, O., Nemazee, D., Ponomarenko, J.V., Sathiamurthy, M., Schoenberger, S., Stewart, S., Surko, P., Way, S., Wilson, S., Sette, A. 2005. The immune epitope database and analysis resource: From vision to blueprint. PLoS Biol 3, e91.
Porter, V. 2011. Bacterial meningitis: A deadly but preventable disease. Prevention: Where do we stand with vaccination efforts? http://www.medscape.com/viewarticle/4810196
Rakesh, S., Pradhan, D., Umamaheswari A. 2009. In silico approach for future development of subunit vaccines against Leptospira interrogans serovar Lai. Int J Bioinform Res 1, 85–92.
Ramakrishnan, M., Ulland, A.J., Steinhardt, L.C., Mösi, J.C., Were, F., Levine, O.S. 2009. Sequelae due to bacterial meningitis among African children: A systematic literature review. BMC Med 14, 47.
Rammensee, H., Bachmann, J., Emmerich, N.P., Bachor, O.A., Stevanovic, S., 1999. SYFPEITHI: Database for MHC ligands and peptide motifs. Immunogenetics 50, 213–219.
Rappuoli, R. 2001. Reverse vaccinology, a genomebased approach to vaccine development. Vaccine 19, 2688–2691.
Saez-Llorens, X., McCracken, G.H.Jr. 2003. Bacterial meningitis in children. Lancet 361, 2139–2148.
Schlech, W.F., Ward, J.I., Band, J.D., Hightower, A., Fraser, D.W., Broome, C.V. 1985. Bacterial meningitis in the United States, 1978 through 1981. The National Bacterial Meningitis Surveillance Study. J Am Med Assoc 253, 1749–1754.
Segal, S., Pollard, A.J. 2004. Vaccines against bacterial meningitis. Brit Med Bull 72, 65–81.
Serruto, D., Rappuoli, R. 2006. Post-genomic vaccine development. FEBS Lett 580, 2985–2992.
Serruto, D., Serino, L., Masignani, V., Pizza, M. 2009. Genome-based approaches to develop vaccines against bacterial pathogens. Vaccine 27, 3245–3250.
Singh, H., Raghava, G.P. 2001. ProPred: Prediction of HLA-DR binding sites. Bioinformatics 17, 1236–1237.
Singh, P., Suman, S., Chandna, S., Das, T.K. 2009. Possible role of amyloid-beta, adenine nucleotide translocase and cyclophilin-D interaction in mitochondrial dysfunction of Alzheimer’s disease. Bioinformation 3, 440–445.
Southwood, S., Sidney, J., Kondo, A., del Guercio, M.F., Appella, E., Hoffman, S., Kubo, R.T., Chesnut, R.W., Grey, H.M., Sette, A. 1998. Several common HLA-DR types share largely overlapping peptide binding repertoires. J Immunol 160, 3363–3373.
Tauber, M.G., Kim, Y.S., Leib, S.L. 1997. Neuronal injury in meningitis. In: Peterson, P.K., Remington, J.S. (Eds.) Defense of the Brain, Blackwell Science, Malden, Mass, 124–143.
Tettelin, H. 2009. The bacterial pan-genome and reverse vaccinology. Genome Dyn 6, 35–47.
Texier, C., Pouvelle, S., Busson, M., Hervé, M., Charron, D., Ménez, A., Maillère B. 2000. HLADR restricted peptide candidates for bee venom immunotherapy. J Immunol 164, 3177–3184.
Thompson, J.D., Gibson, T.J., Plewniak, F., Jeanmougin, F., Higgins, D.G. 1997. The CLUSTAL X windows interface: Flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucl Acid Res 25, 4876–4882.
Tunkel, A.R., Hartman, B.J., Kaplan, S.L., Kaufman, B.A., Roos, K.L., Scheld, W.M., Whitley, R.J. 2004. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39, 1267–1284.
Umamaheswari, A., Pradhan, D., Hemanthkumar, M. 2012. Computer aided subunit vaccine design against pathogenic Leptospira serovars. Interdisciplinary Sci Comput Life Sci 4, 38–45.
Wang, P., Sidney, J., Dow, C., Mothé, B., Sette, A., Peters, B. 2008. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLoS Comput Biol 4, e1000048.
Zagursky, R., Russell, D. 2001. Bioinformatics: Use in bacterial vaccine discovery. Biotechniques 31, 636–659.
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Munikumar, M., Priyadarshini, I.V., Pradhan, D. et al. Computational approaches to identify common subunit vaccine candidates against bacterial meningitis. Interdiscip Sci Comput Life Sci 5, 155–164 (2013). https://doi.org/10.1007/s12539-013-0161-1
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DOI: https://doi.org/10.1007/s12539-013-0161-1
Key words
- bacterial meningitis
- T-cell epitope
- MHC class II molecule
- subunit vaccine
- epitope based docking, molecular dynamics