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Antigenic Properties of Iron Regulated Proteins in Acinetobacter baumannii: An In Silico Approach

  • Hadise Bazmara
  • Iraj RasooliEmail author
  • Abolfazl Jahangiri
  • Fatemeh Sefid
  • Shakiba Darvish Alipour Astaneh
  • Zahra Payandeh
Article

Abstract

Acinetobacter baumannii, an emerging nosocomial pathogen, causes multi-drug and pan-drug resistant infections. This phenomenon necessitates the development of new treatment strategies or vaccines against this pathogen. Iron acquisition systems are important factors for the virulence of pathogenic organisms. Antibodies against iron regulated outer membrane proteins (IROMPs) showed bactericidal and opsonizing activities against A. baumannii in vitro. Data obtained from proteomic studies could be valuable for vaccine design. Comparative proteomic analysis of total lysate and outer membrane fractions isolated from A. baumannii ATCC 19606 cells cultured under iron-rich and chelated conditions resulted in the identification of protein spots differentially produced. Need for bioinformatic tools is imperative for analysis of these data as well as to design novel proteins bearing desired properties. This study undertakes in silico identification of the most effective immunogenic target amongst these iron regulated proteins in A. baumannii which can be employed as a vaccine candidate. Here a screening was carried out on iron- regulated A. baumannii OMPs, based on hydrophilicity, flexibility, beta-turns, solubility and overall antigenic probability. 3D structure of the proteins was modeled. Linear and conformational B cell epitopes predicted and their densities were used for comparison of their immunogenicity. CarO was selected as an efficient immunogenic IROMP in A. baumannii which contributes to sidrophore mediated iron uptake.

Keywords

A. baumanni IROMPs Immunogenicity Epitope density Bioinformatics 3D structure 

Notes

Acknowledgements

The authors wish to thank National Institute for Medical Research Development (NIMAD) Grant No. 958302 and Shahed University for their support to conduct the present study.

Compliance with Ethical Standards

Conflict of interest

We declare no conflict of interests.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Antunes LC, Imperi F, Carattoli A, Visca P (2011) Deciphering the multifactorial nature of Acinetobacter baumanniipathogenicity. PLoS ONE 6:e22674CrossRefGoogle Scholar
  2. Ballouche M, Cornelis P, Baysse C (2009) Iron metabolism: a promising target for antibacterial strategies. Recent Pat Antiinfect Drug Discov 4:190–205CrossRefGoogle Scholar
  3. Benkert P, Tosatto SC, Schomburg D (2008) QMEAN: a comprehensive scoring function for model quality assessment. Proteins 71:261–277CrossRefGoogle Scholar
  4. Cheng J, Randall AZ, Sweredoski MJ, Baldi P (2005) SCRATCH: a protein structure and structural feature prediction server. Nucleic Acids Res 33:W72–W76CrossRefGoogle Scholar
  5. Chiang M-H, Sung W-C, Lien S-P, Chen Y-Z, Lo AF-Y, Huang J-H et al (2015) Identification of novel vaccine candidates against Acinetobacter baumanniiusing reverse vaccinology. Hum Vaccin Immunother 11:1065–1073CrossRefGoogle Scholar
  6. Dallo SF, Denno J, Hong S, Weitao T (2010) Adhesion of Acinetobacter baumanniito extracellular proteins detected by a live cell-protein binding assay. Ethn Dis 20:7Google Scholar
  7. Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform 8:4CrossRefGoogle Scholar
  8. Eijkelkamp BA, Hassan KA, Paulsen IT, Brown MH (2011) Investigation of the human pathogen Acinetobacter baumanniiunder iron limiting conditions. BMC Genom 12:126CrossRefGoogle Scholar
  9. EL-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting linear B-cell epitopes using string kernels. J Mol Recogn 21:243–255CrossRefGoogle Scholar
  10. Goel VK, Kapil A (2001) Monoclonal antibodies against the iron regulated outer membrane proteins of Acinetobacter baumanniiare bactericidal. BMC Microbiol 1:16CrossRefGoogle Scholar
  11. Hassan A, Naz A, Obaid A, Paracha RZ, Naz K, Awan FM et al (2016) Pangenome and immuno-proteomics analysis of Acinetobacter baumanniistrains revealed the core peptide vaccine targets. BMC Genom 17:732CrossRefGoogle Scholar
  12. Haste Andersen P, Nielsen M, Lund O (2006) Prediction of residues in discontinuous B-cell epitopes using protein 3D structures. Protein Sci 15:2558–2567CrossRefGoogle Scholar
  13. Islam AHMS., Singh KKB, Ismail A (2011) Demonstration of an outer membrane protein that is antigenically specific for Acinetobacter baumannii. Diagn Microbiol Infect Dis 69:38–44CrossRefGoogle Scholar
  14. Jahangiri A, Rasooli I, Gargari SLM, Owlia P, Rahbar MR, Amani J et al (2011) An in silico DNA vaccine against Listeria monocytogenes. Vaccine 29:6948–6958CrossRefGoogle Scholar
  15. Jahangiri A, Rasooli I, Rahbar MR, Khalili S, Amani J, Zanoos KA (2012) Precise detection of L. monocytogenes hitting its highly conserved region possessing several specific antibody binding sites. J Theor Biol 305:15–23CrossRefGoogle Scholar
  16. Jahangiri A, Rasooli I, Owlia P, Fooladi AAI, Salimian J (2017a) In silico design of an immunogen against Acinetobacter baumanniibased on a novel model for native structure of outer membrane protein A. Microb Pathog 105:201–210CrossRefGoogle Scholar
  17. Jahangiri A, Amani J, Halabian R (2017b) In silico analyses of staphylococcal enterotoxin B as a DNA vaccine for cancer therapy. Int J Pept Res Ther.  https://doi.org/10.1007/s10989-017-9595-3 Google Scholar
  18. Jin JS, Kwon SO, Moon DC, Gurung M, Lee JH, Kim SI et al (2011) Acinetobacter baumanniisecretes cytotoxic outer membrane protein A via outer membrane vesicles. PLoS ONE 6:e17027CrossRefGoogle Scholar
  19. Kelley LA, Sternberg MJ (2009) Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 4:363–371CrossRefGoogle Scholar
  20. Khalili S, Rahbar MR, Dezfulian MH, Jahangiri A (2015) In silico analyses of Wilms׳ tumor protein to designing a novel multi-epitope DNA vaccine against cancer. J Theor Biol 379:66–78CrossRefGoogle Scholar
  21. Khalili S, Rasaee M, Bamdad T (2017a) 3D structure of DKK1 indicates its involvement in both canonical and non-canonical Wnt pathways. Mol Biol 51:155–166CrossRefGoogle Scholar
  22. Khalili S, Jahangiri A, Hashemi ZS, Khalesi B, Mard-Soltani M, Amani J (2017b) Structural pierce into molecular mechanism underlying Clostridium perfringens epsilon toxin function. Toxicon 127:90–99CrossRefGoogle Scholar
  23. Kim M, Song L, Moon J, Sun ZY, Bershteyn A, Hanson M et al (2013) Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER)segments is dominated by residue accessibility and modulated by stereochemistry. J Biol Chem 288:31888–31901CrossRefGoogle Scholar
  24. Krchnak V, Mach O, Maly A (1987) Computer prediction of potential immunogenic determinants from protein amino acid sequence. Analytical Biochem 165:200–207CrossRefGoogle Scholar
  25. Kringelum JV, Lundegaard C, Lund O, Nielsen M (2012) Reliable B cell epitope predictions: impacts of method development and improved benchmarking. PLoS Comput Biol 8:e1002829CrossRefGoogle Scholar
  26. Lambert C, Leonard N, De Bolle X, Depiereux E (2002) ESyPred3D: prediction of proteins 3D structures. Bioinformatics 18:1250–1256CrossRefGoogle Scholar
  27. Lee Y, Kim CK, Lee H, Jeong SH, Yong D, Lee K (2011) A novel insertion sequence, ISAba10, inserted into ISAba1 adjacent to the blaOXA-23 gene and disrupting the outer membrane protein gene carO in Acinetobacter baumannii. Antimicrob Agents Chemother 55:361–363CrossRefGoogle Scholar
  28. Liu W, Chen Y (2005) High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of monomeric proteins. Eur J Immunol 35:505–514CrossRefGoogle Scholar
  29. Liu W, Peng Z, Liu Z, Lu Y, Ding J, Chen YH (2004) High epitope density in a single recombinant protein molecule of the extracellular domain of influenza A virus M2 protein significantly enhances protective immunity. Vaccine 23:366–371CrossRefGoogle Scholar
  30. Luo G, Lin L, Ibrahim AS, Baquir B, Pantapalangkoor P, Bonomo RA et al (2012) Active and passive immunization protects against lethal, extreme drug resistant-Acinetobacter baumanniiinfection. PLoS ONE 7:e29446CrossRefGoogle Scholar
  31. Magnan CN, Randall A, Baldi P (2009) SOLpro: accurate sequence-based prediction of protein solubility. Bioinformatics 25:2200–2207CrossRefGoogle Scholar
  32. McConnell MJ, Rumbo C, Bou G, Pachón J (2011a) Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii. Vaccine 29:5705–5710CrossRefGoogle Scholar
  33. McConnell MJ, Domínguez-Herrera J, Smani Y, López-Rojas R, Docobo-Pérez F, Pachón J (2011b) Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistantAcinetobacter baumannii. Infection immunity 79:518–526CrossRefGoogle Scholar
  34. Mohammadpour H, Pourfathollah AA, Zarif MN, Khalili S (2016) Key role of Dkk3 protein in inhibition of cancer cell proliferation: an in silico identification. J Theor Biol 393:98–104CrossRefGoogle Scholar
  35. Moriel DG, Beatson SA, Wurpel DlJ, Lipman J, Nimmo GR, Paterson DL et al (2013) Identification of novel vaccine candidates against multidrug-resistant Acinetobacter baumannii. PLoS ONE 8:e77631CrossRefGoogle Scholar
  36. Mortensen BL, Skaar EP (2012) Host-microbe interactions that shape the pathogenesis of Acinetobacter baumanniiinfection. Cell Microbiol 14:1336–1344CrossRefGoogle Scholar
  37. Mussi MA, Relling VnM, Limansky AS, Viale AM (2007) CarO, an Acinetobacter baumanniiouter membrane protein involved in carbapenem resistance, is essential for lGÇÉornithine uptake. FEBS Lett 581:5573–5578CrossRefGoogle Scholar
  38. Mussi MA, Limansky AS, Relling V, Ravasi P, Arakaki A, Actis LA et al (2011) Horizontal gene transfer/assortative recombination within the Acinetobacter baumanniiclinical population provides genetic diversity at the single carO gene encoding a major outer membrane protein channel. J Bacteriol 193:4736CrossRefGoogle Scholar
  39. Negahdaripour M, Eslami M, Nezafat N, Hajighahramani N, Ghoshoon MB, Shoolian E et al (2017) A novel HPV prophylactic peptide vaccine, designed by immunoinformatics and structural vaccinology approaches. Infect Genet Evol 54:402–416CrossRefGoogle Scholar
  40. Nezafat N, Eslami M, Negahdaripour M, Rahbar MR, Ghasemi Y (2017) Designing an efficient multi-epitope oral vaccine against Helicobacter pyloriusing immunoinformatics and structural vaccinology approaches. Mol BioSyst 13:699–713CrossRefGoogle Scholar
  41. Ni Z, Chen Y, Ong E, He Y (2017) Antibiotic resistance determinant-focused Acinetobacter baumanniivaccine designed using reverse vaccinology. Int J Mol Sci 18:458CrossRefGoogle Scholar
  42. Nwugo CC, Gaddy JA, Zimbler DL, Actis LA (2011) Deciphering the iron response in Acinetobacter baumannii: a proteomics approach. J Proteom 74:44–58CrossRefGoogle Scholar
  43. Ponomarenko J, Bui HH, Li W, Fusseder N, Bourne PE, Sette A et al (2008) ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC Bioinform 9:514CrossRefGoogle Scholar
  44. Prasad T, Chandra A, Mukhopadhyay CK, Prasad R (2006) Unexpected link between iron and drug resistance of Candidaspp.: iron depletion enhances membrane fluidity and drug diffusion, leading to drug-susceptible cells. Antimicrobial Agents Chemother 50:3597–3606CrossRefGoogle Scholar
  45. Rahbar MR, Rasooli I, Gargari SLM, Amani J, Fattahian Y (2010) In silico analysis of antibody triggering biofilm associated protein in Acinetobacter baumannii. J Theor Biol 266:275–290CrossRefGoogle Scholar
  46. Rahbar MR, Rasooli I, Gargari SLM, Sandstrom G, Amani J, Fattahian Y et al (2012) A potential in silico antibody-antigen based diagnostic test for precise identification of Acinetobacter baumannii. J Theor Biol 294:29–39CrossRefGoogle Scholar
  47. Reimer U (2009) Prediction of linear B-cell epitopes. In: Schutkowski M, Reineke U (eds) Epitope mapping protocols, 2nd edn. Springer, New York, pp 335–344CrossRefGoogle Scholar
  48. Rinaudo CD, Telford JL, Rappuoli R, Seib KL (2009) Vaccinology in the genome era. J Clin Investig 119:2515–2525CrossRefGoogle Scholar
  49. Roy A, Kucukural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5:725–738CrossRefGoogle Scholar
  50. Sefid F, Rasooli I, Jahangiri A (2013) In silico determination and validation of baumannii acinetobactin utilization a structure and ligand binding site. BioMed Res Int.  https://doi.org/10.1155/2013/172784 Google Scholar
  51. Sefid F, Rasooli I, Jahangiri A, Bazmara H (2015) Functional exposed amino acids of BauA as potential immunogen against Acinetobacter baumannii. Acta Biotheor 63:129–149CrossRefGoogle Scholar
  52. Singh R, Garg N, Shukla G, Capalash N, Sharma P (2016) Immunoprotective efficacy of Acinetobacter baumanniiouter membrane protein, FilF, predicted in silico as a potential vaccine candidate. Front Microbiol.  https://doi.org/10.3389/fmicb.2016.00158 Google Scholar
  53. Smialowski P, Martin-Galiano AJ, Mikolajka A, Girschick T, Holak TA, Frishman D (2007) Protein solubility: sequence based prediction and experimental verification. Bioinformatics 23:2536–2542CrossRefGoogle Scholar
  54. Sun J, Wu D, Xu T, Wang X, Xu X, Tao L et al (2009) SEPPA: a computational server for spatial epitope prediction of protein antigens. Nucleic Acids Res 37:W612–W616CrossRefGoogle Scholar
  55. Tong Y, Guo M (2009) Bacterial heme-transport proteins and their heme-coordination modes. Arch Biochem Biophys 481:1–15CrossRefGoogle Scholar
  56. Toobak H, Rasooli I, Talei D, Jahangiri A, Owlia P, Astaneh SDA (2013a) Immune response variations to Salmonella entericaserovar Typhi recombinant porin proteins in mice. Biologicals 41:224–230CrossRefGoogle Scholar
  57. Toobak H, Rasooli I, Gargari SLM, Jahangiri A, Nadoushan MJ, Owlia P et al (2013b) Characterization of the Salmonella typhi outer membrane protein C. Microbiol Biotechnol Lett 41:128–134CrossRefGoogle Scholar
  58. Vivona S, Bernante F, Filippini F (2006) NERVE: new enhanced reverse vaccinology environment. BMC Biotechnol 6:35CrossRefGoogle Scholar
  59. Yasser EM, Honavar V (2010) Recent advances in B-cell epitope prediction methods. Immun Res 6:S2Google Scholar
  60. Yasser EM, Dobbs D, Honavar V (2008) Predicting flexible length linear B-cell epitopes. Comput Syst Bioinform Conf 7:121Google Scholar
  61. Zhang Q, Wang P, Kim Y, Haste-Andersen P, Beaver J, Bourne PE et al (2008) Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res 36:W513–W518CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Hadise Bazmara
    • 1
  • Iraj Rasooli
    • 1
    • 2
    Email author
  • Abolfazl Jahangiri
    • 1
    • 3
  • Fatemeh Sefid
    • 4
  • Shakiba Darvish Alipour Astaneh
    • 5
  • Zahra Payandeh
    • 6
  1. 1.Department of BiologyShahed UniversityTehranIran
  2. 2.Molecular Microbiology Research CenterShahed UniversityTehranIran
  3. 3.Applied Microbiology Research CenterBaqiyatallah University of Medical SciencesTehranIran
  4. 4.Department of BiologyScience and Art UniversityYazdIran
  5. 5.Department of BiotechnologySemnan UniversitySemnanIran
  6. 6.Department of Medical Biotechnology and Nanotechnology, Faculty of MedicineZanjan University of Medical SciencesZanjanIran

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