Immunogenic effect of PLGA nanoparticles containing Klebsiella pneumoniae K2O1 capsule antigen against urinary tract infection in BALB/C mice

Document Type : Original Article

Authors

1 Department of Microbiology, Faculty of Science, Islamic Azad University Qom Branch, Qom, Iran

2 Departman of Microbiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran

3 Recombinant Vaccine Research Center, Tehran University of Sciences, Tehran, Iran

4 Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Science, Zanjan, Iran

Abstract

Background and Objective: Klebsiella can cause urinary tract infections that is associated with drug resistance. Capsule production as a means of resistance can prevent host immune system responses. This study investigated the effect of a PLGA nanoparticles vaccine containing capsule antigen.
Materials and Methods: Vaccination of 20 mice with an age of 3-5 weeks (with a weight range of 22±18 g) was performed in four groups of capsules, PLGA, PLGA-capsule combination (PLGA+CPS) and control (PBS). In this study, the fabrication of nanoparticles was investigated by zetasizer and FITR tests. Microbial loading was also performed on the bladder.One-way analysis of variance and Tukey post hoc test were used for statistical analysis .
Results: The results of confirmation tests of zetaiser showed that the nanoparticle size and the size of PLGA nanoparticles containing capsule antigen molecule were 178.7 and 159.4 nm, respectively.The result of FTIR and the shapes of the corresponding peaks confirmed the presence of antigen functional groups in the nanoparticle structure and the formation of ester bonds.The resut of FTIR test also indicates the success of PLGA nanoparticles containing capsule antigen , the results of microbial challenge showed that in the control and PLGA groups, due to the fact that PLGA nanoparticles vaccine contain capsule antigen were not used, a significant increase was observed in terms of the number of colonies compared to other groups  )p<0/05( .
Conclusion: PLGA nanoparticles containing capsule antigen molecules have a better ability than pure capsules and can significantly reduce tissue damage.

Keywords


  1. Agyeman AA, Bergen PJ, Rao GG, Nation RL, Landersdorfer CB. A systematic review and meta-analysis of treatment outcomes following antibiotic therapy among patients with carbapenem-resistant Klebsiella pneumoniae infections. International Journal of Antimicrobial Agents 2020 ;55(1):105833. doi:10.1016/j.ijantimicag.2019.10.014.
  2. Martin RM, Bachman MA. Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Frontiers in Cellular and Infection Microbiology 2018; 8:4. doi:10.3389/fcimb.2018.00004.
  3. Zhu WM, Yuan Z, Zhou HY. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection relative to two types of control patients: a systematic review and meta-analysis. Antimicrobial Resistance & Infection Control 2020;9(1):1-3. doi:10.1186/s13756-020-0686-0. 
  4. Wu D, Huang X, Jia C, Liu J, Wan Q. Clinical manifestation, distribution, and drug resistance of pathogens among abdominal solid organ transplant recipients with Klebsiella pneumoniae infections. InTransplantation proceedings 2020 :289-294. doi:10.1016/j.transproceed.2019.11.023
  5. Choi M, Hegerle N, Nkeze J, Sen S, Jamindar S, Nasrin S, et al. The diversity of lipopolysaccharide (o) and capsular polysaccharide (K) antigens of invasive Klebsiella pneumoniae in a Multi-Country collection. Frontiers in Microbiology 2020;   11:1249. doi:10.3389/fmicb.2020.01249.
  6. Adwan GM, Owda DM, Abu-Hijleh AA. Prevalence of Capsular Polysaccharide Genes and Antibiotic Resistance Pattern of Klebsiella pneumoniae in Palestine. Jordan Journal of Biological Sciences 2020  ;13(4).
  7. Li B, Zhao Y, Liu C, Chen Z, Zhou D. Molecular pathogenesis of Klebsiella pneumoniae. Future Microbiology 2014 ;9(9):1071-81. doi:10.2217/fmb.14.48.
  8. Williams P, Lambert PA, Brown MR, Jones RJ. The role of the O and K antigens in determining the resistance of Klebsiella aerogenes to serum killing and phagocytosis. Microbiology 1983 ;129(7):2181-91. doi:10.1099/00221287-129-7-2181.
  9. Xu Y, Zhang J, Wang M, Liu M, Liu G, Qu H, Liu J, Deng Z, Sun J, Ou HY, Qu J. Mobilization of the nonconjugative virulence plasmid from hypervirulent Klebsiella pneumoniae. Genome Medicine. 2021;13(1):1-5. doi:10.1186/s13073-021-00936-5.
  10. Athamna AB, Ofek IT, Keisari Y, Markowitz S, Dutton GG, Sharon N. Lectinophagocytosis of encapsulated Klebsiella pneumoniae mediated by surface lectins of guinea pig alveolar macrophages and human monocyte-derived macrophages. Infection and Immunity 1991 ;59(5):1673-82. doi:10.1128/iai.59.5.
  11. Khurana S, Utreja P, Tiwary AK, Jain NK, Jain S. Nanostructured lipid carriers and their application in drug delivery. International Journal of Biomedical Engineering and Technology 2009;  2(2):152-71. doi:10.1504/IJBET.2009.022913.
  12. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and surfaces B: biointerfaces 2010;75(1):1-8. doi:10.1016/j.colsurfb.2009.09.001.
  13. Ghitman J, Biru EI, Stan R, Iovu H. Review of hybrid PLGA nanoparticles: Future of smart drug delivery and theranostics medicine. Materials & Design 2020 ;193:108805. doi:10.1016/j.matdes.2020.108805.
  14. Sahu R, Dixit S, Verma R, Duncan SA, Coats MT, Giambartolomei GH, Singh SR, Dennis VA. A nanovaccine formulation of Chlamydia recombinant MOMP encapsulated in PLGA 85: 15 nanoparticles augments CD4+ effector (CD44high CD62Llow) and memory (CD44high CD62Lhigh) T-cells in immunized mice. Nanomedicine: Nanotechnology, Biology and Medicine 2020 ;29:102257. doi:10.1016/j.nano.2020.102257.
  15. Jamkhande PG, Ghule NW, Bamer AH, Kalaskar MG. Metal nanoparticles synthesis: An overview on methods of preparation, advantages and disadvantages, and applications. Journal of Drug Delivery Science and Technology 2019 ;53:101174. doi:10.1016/j.jddst.2019.101174.
  16. Ding D, Zhu Q. Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular therapeutics. Materials Science and Engineering: C 2018 ;92:1041-60. doi:10.1016/j.msec.2017.12.036.
  17. Song X, Zhao X, Zhou Y, Li S, Ma Q. Pharmacokinetics and disposition of various drug loaded biodegradable poly (lactide-co-glycolide)(PLGA) nanoparticles. Current drug metabolism. 2010 ;11(10):859-69.doi:10.2174/138920010794479682.
  18. Tabatabaei Mirakabad FS, Nejati-Koshki K, Akbarzadeh A, Yamchi MR, Milani M, Zarghami N, Zeighamian V, Rahimzadeh A, Alimohammadi S, Hanifehpour Y, Joo SW. PLGA-based nanoparticles as cancer drug delivery systems. Asian Pacific Journal of Cancer Prevention 2014;15(2):517-35.doi:10.7314/APJCP.2014.15.2.517.
  19. Feray A, Szely N, Guillet E, Hullo M, Legrand FX, Brun E, Pallardy M, Biola-Vidamment A. How to Address the Adjuvant Effects of Nanoparticles on the Immune System. Nanomaterials 2020;10(3):425.doi:10.3390/nano10030425.
  20. Badkas A, Frank E, Zhou Z, Jafari M, Chandra H, Sriram V, Lee JY, Yadav JS. Modulation of in vitro phagocytic uptake and immunogenicity potential of modified Herceptin®-PLGA nanoparticles contain capsule antigen PLGA-PEG nanoparticles for drug delivery. Colloids and Surfaces B: Biointerfaces 2018:271-8. doi:10.1016/j.colsurfb.2017.12.001.
  21. Li H, Wang J, Zhou T, Zhang Y, Zhang Z. An investigation of the effects of nanosize delivery system for antisense oligonucleotide on esophageal squamous cancer cells. Cancer Biology & Therapy 2008 ;7(11):1852-9. doi:10.4161/cbt.7.11.6879.
  22. Fischer S, Schlosser E, Mueller M, Csaba N, Merkle HP, Groettrup M, Gander B. Concomitant delivery of a CTL-restricted peptide antigen and CpG ODN by PLGA microparticles induces cellular immune response. Journal of Drug Targeting 2009 ;17(8):652-61. doi:10.1080/1061186090311965 6.
  23. Taha MA, Singh SR, Dennis VA. Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide. Nanotechnology 2012;23(32):325101. doi:10.1088/0957-4484/23/32/325101/meta.
  24. Zhang K, Tang X, Zhang J, Lu W, Lin X, Zhang Y, Tian B, Yang H, He H. PEG–PLGA copolymers: Their structure and structure-influenced drug delivery applications. Journal of Controlled Release 2014:77-86. doi:10.1016/j.jconrel.2014.03.026.
  25. Bandyopadhyay A, Fine RL, Demento S, Bockenstedt LK, Fahmy TM. The impact of nanoparticle ligand density on dendritic-cell targeted vaccines. Biomaterials 2011 ;32(11):3094-105. doi:10.1016/j.biomaterials.2010.12.054.
  26. Simón-Yarza T, Tamayo E, Benavides C, Lana H, Formiga FR, Grama CN, et al. Functional benefits of PLGA particulates carrying VEGF and CoQ10 in an animal of myocardial ischemia. International Journal of Pharmaceutics 2013;454(2):784-90. doi:10.1016/j.ijpharm.2013.04.015.
  27. He Z, Shi Z, Sun W, Ma J, Xia J, Zhang X, et al. Hemocompatibility of folic-acid-PLGA nanoparticles contain capsule antigen amphiphilic PEG-PLGA copolymer nanoparticles for co-delivery of cisplatin and paclitaxel: treatment effects for non-small-cell lung cancer. Tumor Biology 2016; 37(6):7809-21. doi:10.1007/s13277-015-4634-1.