Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Immunoinformatic Approach for the Identification of Potential Epitopes Against Stenotrophomonas maltophilia: A Global Opportunistic Pathogen

Author(s): Pragathi Ravilla Basker and Shobana Sugumar*

Volume 18, Issue 5, 2021

Published on: 09 November, 2020

Page: [454 - 460] Pages: 7

DOI: 10.2174/1570180817999201109202557

Price: $65

Abstract

Background: Stenotrophomonas maltophilia is an aerobic, non-fermentative, gram negative, multidrug resistant and opportunistic nosocomial pathogen. It is associated with high morbidity and mortality in severely immunocompromised paediatric patients, including neonates. Immunoinformatic analysis paved a new way to design epitope-based vaccines which resulted in a potential immunogen with advantages such as lower cost, specific immunity, ease of production, devoid of side effects, and less time consumption than conventional vaccines. Till date, there is no development in the vaccines or antibody-based treatments for S. maltophilia-associated infections.

Introduction: Currently, epitope-based peptide vaccines against pathogenic bacteria have grasped more attention. In our present study, we have utilized various immunoinformatic tools to find a prominent epitope that interacts with the maximum number of HLA alleles and also with the maximum population coverage for developing a vaccine against Stenotrophomonas maltophilia.

Methods: This study has incorporated an immunoinformatic based screening approach to explore potential epitope-based vaccine candidates in Stenotrophomonas maltophilia proteome. In this study, 4365 proteins of the Stenotrophomonas maltophilia K279a proteome were screened to identify potential antigens that could be used as a good candidate for the vaccine. Various immunoinformatic tools were used to predict the binding of the promiscuous epitopes with Major Histocompatibility Complex (MHC) class I molecules. Other properties such as allergenicity, physiochemical properties, adhesion properties, antigenicity, population coverage, epitope conservancy and toxicity were analysed for the predicted epitope.

Results: This study helps in finding the prominent epitope in Stenotrophomonas infections. Hence, the main objective in this research was to screen complete Stenotrophomonas maltophilia proteome to recognize putative epitope candidates for vaccine design. Using computational vaccinology and immunoinformatic tools approach, several aspects are obligatory to be fulfilled by an epitope to be considered as a vaccine candidate. Our findings were promising and showed that the predicted epitopes were non-allergenic and fulfilled other parameters required for being a suitable candidate based on certain physio-chemical, antigenic and adhesion properties.

Conclusion: The epitopes LLFVLCWPL and KSGEGKCGA have shown the highest binding score of −103 and −78.1 kcal/mol with HLA-A*0201 and HLA-B*0702 MHC class I allele, respectively. They were also predicted to be immunogenic and non-allergenic. Further various immunological tests, both in vivo and in vitro methods, should be performed for finding the efficiency of the predicted epitope in the development of a targeted vaccine against Stenotrophomonas maltophilia infection.

Keywords: Stenotrophomonas maltophilia, epitope-based vaccine, immunoinformatics, epitope prediction, docking, HLA alleles.

Graphical Abstract

[1]
Al-Anazi, K.A.; Al-Jasser, A.M. Infections caused by Stenotrophomonas maltophilia in recipients of hematopoietic stem cell transplantation. Front. Oncol., 2014, 4, 232.
[http://dx.doi.org/10.3389/fonc.2014.00232] [PMID: 25202682]
[2]
Jeon, Y.D.; Jeong, W.Y.; Kim, M.H.; Jung, I.Y.; Ahn, M.Y.; Ann, H.W.; Ahn, J.Y.; Han, S.H.; Choi, J.Y.; Song, Y.G.; Kim, J.M.; Ku, N.S. Risk factors for mortality in patients with Stenotrophomonas maltophilia bacteremia. Medicine (Baltimore), 2016, 95(31), e4375.
[http://dx.doi.org/10.1097/MD.0000000000004375] [PMID: 27495046]
[3]
Brooke, J.S.; Di Bonaventura, G.; Berg, G.; Martinez, J.L. A multidisciplinary look at Stenotrophomonas maltophilia: An emerging multi-drug-resistant global opportunistic pathogen. Front. Microbiol., 2017, 8, 1511.
[http://dx.doi.org/10.3389/fmicb.2017.01511] [PMID: 28912755]
[4]
Rizek, C.F.; Jonas, D.; Garcia Paez, J.I.; Rosa, J.F.; Perdigão Neto, L.V.; Martins, R.R.; Moreno, L.Z.; Rossi, A., Junior; Levin, A.S.; Costa, S.F. Multidrug-resistant Stenotrophomonas maltophilia: Description of new MLST profiles and resistance and virulence genes using whole-genome sequencing. J. Glob. Antimicrob. Resist., 2018, 15, 212-214.
[http://dx.doi.org/10.1016/j.jgar.2018.07.009] [PMID: 30036694]
[5]
Falagas, M.E.; Kastoris, A.C.; Vouloumanou, E.K.; Dimopoulos, G. Community-acquired Stenotrophomonas maltophilia infections: a systematic review. Eur. J. Clin. Microbiol. Infect. Dis., 2009, 28(7), 719-730. [a]
[6]
Looney, W.J.; Narita, M.; Mühlemann, K. Stenotrophomonas maltophilia: An emerging opportunist human pathogen. Lancet Infect. Dis., 2009, 9(5), 312-323.
[http://dx.doi.org/10.1016/S1473-3099(09)70083-0] [PMID: 19393961]
[7]
Jones, R.N.; Sader, H.S.; Beach, M.L. Contemporary in vitro spectrum of activity summary for antimicrobial agents tested against 18569 strains non-fermentative Gram-negative bacilli isolated in the SENTRY Antimicrobial Surveillance Program (1997-2001). Int. J. Antimicrob. Agents, 2003, 22(6), 551-556.
[http://dx.doi.org/10.1016/S0924-8579(03)00245-0] [PMID: 14659650]
[8]
Jagevall, S; Rabe, L; Pedersen, K Abundance and diversity of biofilms in natural and artificial aquifers of the A¨spö Hard Rock Laboratory Microb. Ecol. 61:410 Sweden., 2011, 422.
[9]
Jang, T.N.; Wang, F.D.; Wang, L.S.; Liu, C.Y.; Liu, I.M. Xanthomonas maltophilia bacteremia: An analysis of 32 cases. J. Formos. Med. Assoc., 1992, 91(12), 1170-1176.
[PMID: 1363639]
[10]
Victor, M.A.; Arpi, M.; Bruun, B.; Jønsson, V.; Hansen, M.M. Xanthomonas maltophilia bacteremia in immunocompromised hematological patients. Scand. J. Infect. Dis., 1994, 26(2), 163-170.
[http://dx.doi.org/10.3109/00365549409011780] [PMID: 8036472]
[11]
Saino, Y.; Inoue, M.; Mitsuhashi, S. Purification and properties of an inducible cephalosporinase from Pseudomonas maltophilia GN12873. Antimicrob. Agents Chemother., 1984, 25(3), 362-365.
[http://dx.doi.org/10.1128/AAC.25.3.362] [PMID: 6609682]
[12]
Saino, Y.; Kobayashi, F.; Inoue, M.; Mitsuhashi, S. Purification and properties of inducible penicillin beta-lactamase isolated from Pseudomonas maltophilia. Antimicrob. Agents Chemother., 1982, 22(4), 564-570.
[http://dx.doi.org/10.1128/AAC.22.4.564] [PMID: 6983856]
[13]
Hotta, G.; Matsumura, Y.; Kato, K.; Nakano, S.; Yunoki, T.; Yamamoto, M.; Nagao, M.; Ito, Y.; Takakura, S.; Ichiyama, S. Risk factors and outcomes of Stenotrophomonas maltophilia bacteraemia: A comparison with bacteraemia caused by Pseudomonas aeruginosa and Acinetobacter species. PLoS One, 2014, 9(11), e112208.
[http://dx.doi.org/10.1371/journal.pone.0112208] [PMID: 25375244]
[14]
Looney, W.J. Role of Stenotrophomonas maltophilia in hospital-acquired infection. Br. J. Biomed. Sci., 2005, 62(3), 145-154.
[http://dx.doi.org/10.1080/09674845.2005.11732702] [PMID: 16196464]
[15]
Abbott, I.J.; Slavin, M.A.; Turnidge, J.D.; Thursky, K.A.; Worth, L.J. Stenotrophomonas maltophilia: Emerging disease patterns and challenges for treatment. Expert Rev. Anti Infect. Ther., 2011, 9(4), 471-488.
[http://dx.doi.org/10.1586/eri.11.24] [PMID: 21504403]
[16]
Brooke, J.S. Stenotrophomonas maltophilia: An emerging global opportunistic pathogen. Clin. Microbiol. Rev., 2012, 25(1), 2-41.
[http://dx.doi.org/10.1128/CMR.00019-11] [PMID: 22232370]
[17]
Falagas, M.E.; Valkimadi, P.E.; Huang, Y.T.; Matthaiou, D.K.; Hsueh, P.R. Therapeutic options for Stenotrophomonas maltophilia infections beyond co-trimoxazole: A systematic review. J. Antimicrob. Chemother., 2008, 62(5), 889-894.
[http://dx.doi.org/10.1093/jac/dkn301] [PMID: 18662945]
[18]
Singhal, L.; Kaur, P.; Gautam, V. Stenotrophomonas maltophilia: From trivial to grievous. Indian J. Med. Microbiol., 2017, 35(4), 469-479.
[http://dx.doi.org/10.4103/ijmm.IJMM_16_430] [PMID: 29405136]
[19]
Gasteiger, E.; Hoogland, C.; Gattiker, A.; Wilkins, M.R.; Appel, R.D.; Bairoch, A. Protein identification and analysis tools on the ExPASy server. The proteomics protocols handbook; Humana press, 2005, pp. 571-607.
[http://dx.doi.org/10.1385/1-59259-890-0:571]
[20]
Sbai, H.; Mehta, A.; DeGroot, A.S. Use of T cell epitopes for vaccine development. Curr. Drug Targets Infect. Disord., 2001, 1(3), 303-313.
[http://dx.doi.org/10.2174/1568005014605955] [PMID: 12455403]
[21]
Tang, H.; Liu, X.S.; Fang, Y.Z.; Pan, L.; Zhang, Z.W. The epitopes of foot and mouth disease. Asian J. Anim. Vet. Adv., 2012, 7, 1261-1265.
[http://dx.doi.org/10.3923/ajava.2012.1261.1265]
[22]
Crossman, L.C.; Gould, V.C.; Dow, J.M.; Vernikos, G.S.; Okazaki, A.; Sebaihia, M.; Saunders, D.; Arrowsmith, C.; Carver, T.; Peters, N.; Adlem, E.; Kerhornou, A.; Lord, A.; Murphy, L.; Seeger, K.; Squares, R.; Rutter, S.; Quail, M.A.; Rajandream, M.A.; Harris, D.; Churcher, C.; Bentley, S.D.; Parkhill, J.; Thomson, N.R.; Avison, M.B. The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol., 2008, 9(4), R74.
[http://dx.doi.org/10.1186/gb-2008-9-4-r74] [PMID: 18419807]
[23]
Doytchinova, I.A.; Flower, D.R. VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics, 2007, 8(1), 4.
[http://dx.doi.org/10.1186/1471-2105-8-4] [PMID: 17207271]
[24]
Dimitrov, I.; Naneva, L.; Doytchinova, I.; Bangov, I. AllergenFP: allergenicity prediction by descriptor fingerprints. Bioinformatics, 2014, 30(6), 846-851.
[http://dx.doi.org/10.1093/bioinformatics/btt619] [PMID: 24167156]
[25]
Sachdeva, G.; Kumar, K.; Jain, P.; Ramachandran, S. SPAAN: A software program for prediction of adhesins and adhesin-like proteins using neural networks. Bioinformatics, 2005, 21(4), 483-491.
[http://dx.doi.org/10.1093/bioinformatics/bti028] [PMID: 15374866]
[26]
Yu, N.Y.; Wagner, J.R.; Laird, M.R.; Melli, G.; Rey, S.; Lo, R.; Dao, P.; Sahinalp, S.C.; Ester, M.; Foster, L.J.; Brinkman, F.S. PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics, 2010, 26(13), 1608-1615.
[http://dx.doi.org/10.1093/bioinformatics/btq249] [PMID: 20472543]
[27]
Krogh, A.; Larsson, B.; von Heijne, G.; Sonnhammer, E.L. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J. Mol. Biol., 2001, 305(3), 567-580.
[http://dx.doi.org/10.1006/jmbi.2000.4315] [PMID: 11152613]
[28]
Singh, H.; Raghava, G.P.S. Propred I: prediction of HLA class-I binding sites. Bioinformatics, 2003, 19, 1009-1014.
[http://dx.doi.org/10.1093/bioinformatics/btg108] [PMID: 12761064]
[29]
Singh, A.; Mitra, M.; Sampath, G.; Venugopal, P.; Rao, J.V.; Krishnamurthy, B.; Gupta, M.K.; Sri Krishna, S.; Sudhakar, B.; Rao, N.B.; Kaushik, Y.; Gopinathan, K.; Hegde, N.R.; Gore, M.M.; Krishna Mohan, V.; Ella, K.M. A Japanese encephalitis vaccine from India induces durable and cross-protective immunity against temporally and spatially wide-ranging global field strains. J. Infect. Dis., 2015, 212(5), 715-725.
[http://dx.doi.org/10.1093/infdis/jiv023] [PMID: 25601942]
[30]
Ansari, H.R.; Flower, D.R.; Raghava, G.P.S. AntigenDB: an immunoinformatics database of pathogen antigens. Nucleic Acids Res., 2010, 38(Database issue), D847-D853.
[http://dx.doi.org/10.1093/nar/gkp830] [PMID: 19820110]
[31]
Bui, H.H.; Sidney, J.; Dinh, K.; Southwood, S.; Newman, M.J.; Sette, A. Predicting population coverage of T-cell epitope-based diagnostics and vaccines. BMC Bioinformatics, 2006, 7, 153.
[http://dx.doi.org/10.1186/1471-2105-7-153] [PMID: 16545123]
[32]
Kaur, H.; Garg, A.; Raghava, G.P.S. PEPstr: A de novo method for tertiary structure prediction of small bioactive peptides. Protein Pept. Lett., 2007, 14(7), 626-631.
[http://dx.doi.org/10.2174/092986607781483859] [PMID: 17897087]
[33]
Lovell, S.C.; Davis, I.W.; Arendall, W.B., III; de Bakker, P.I.W.; Word, J.M.; Prisant, M.G.; Richardson, J.S.; Richardson, D.C. Structure validation by Calpha geometry: Phi,psi and Cbeta deviation. Proteins, 2003, 50(3), 437-450.
[http://dx.doi.org/10.1002/prot.10286] [PMID: 12557186]
[34]
Yang, J.M.; Chen, C.C. GEMDOCK: A generic evolutionary method for molecular docking. Proteins, 2004, 55(2), 288-304.
[http://dx.doi.org/10.1002/prot.20035] [PMID: 15048822]
[35]
Vivona, S.; Gardy, J.L.; Ramachandran, S.; Brinkman, F.S.; Raghava, G.P.S.; Flower, D.R.; Filippini, F. Computer-aided biotechnology: from immuno-informatics to reverse vaccinology. Trends Biotechnol., 2008, 26(4), 190-200.
[http://dx.doi.org/10.1016/j.tibtech.2007.12.006] [PMID: 18291542]
[36]
Wang, C.H.; Yu, C.M.; Hsu, S.T.; Wu, R.X. Levofloxacin-resistant Stenotrophomonas maltophilia: Risk factors and antibiotic susceptibility patterns in hospitalized patients. J. Hosp. Infect., 2020, 104(1), 46-52.
[http://dx.doi.org/10.1016/j.jhin.2019.09.001] [PMID: 31505224]
[37]
Chakrabarty, R.P.; Alam, A.S.M.R.U.; Shill, D.K.; Rahman, A. Identification and qualitative characterization of new therapeutic targets in Stenotrophomonas maltophilia through in silico proteome exploration. Microb. Pathog., 2020, 149, 104293.
[http://dx.doi.org/10.1016/j.micpath.2020.104293] [PMID: 32531498]
[38]
Murugan, N.A.; Pandian, C.J.; Jeyakanthan, J. Computational investigation on Andrographis paniculata phytochemicals to evaluate their potency against SARS-CoV-2 in comparison to known antiviral compounds in drug trials. J. Biomol. Struct. Dyn., 2020, 1-12.
[http://dx.doi.org/10.1080/07391102.2020.1777901] [PMID: 32543978]
[39]
Serruto, D.; Bottomley, M.J.; Ram, S.; Giuliani, M.M.; Rappuoli, R. The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: Immunological, functional and structural characterization of the antigens. Vaccine, 2012, 30(Suppl. 2), B87-B97.
[http://dx.doi.org/10.1016/j.vaccine.2012.01.033] [PMID: 22607904]
[40]
Khan, S.; Khan, A.; Rehman, A.U.; Ahmad, I.; Ullah, S.; Khan, A.A.; Ali, S.S.; Afridi, S.G.; Wei, D.Q. Immunoinformatics and structural vaccinology driven prediction of multi-epitope vaccine against Mayaro virus and validation through in-silico expression. Infect. Genet. Evol., 2019, 73, 390-400.
[http://dx.doi.org/10.1016/j.meegid.2019.06.006] [PMID: 31173935]

© 2024 Bentham Science Publishers | Privacy Policy