Study of the pharmacodynamics of technology for treating resistant bacterial infections using quantum dots

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Background. Antimicrobial resistance, particularly multidrug-resistant and extensively drug-resistant strains, poses a major health threat worldwide, causing approximately 1.3 million deaths annually. This trend dictates the need to search for new approaches to the treatment of diseases initiated by strains of antibiotic-resistant microflora. In recent years, one of the promising areas in this area is the study of the anti-infectious activity of nanoparticles, in particular quantum dots (QDs). The mechanisms of anti-infective activity of QDs are determined by their ability to penetrate into the bacterial cell due to their ultra-small size (3–5 nm) and destroy it due to the dosed production of reactive oxygen species, which are coupled with free electron pairs at the external energy level of QDs.

Objective. Evaluation of the pharmacodynamics of metal nanoparticles (QDs) during interaction with a bacterial cell to determine the potential prospects for treating resistant bacterial infections.

Methods. Scanning and transmission electron microscopy was used as a method to study the characteristics of the pharmacodynamics of QDs during interaction with a bacterial cell. The objects of study included 0.001% aqueous solution of InP/ZnSe/ZnS metal QDs (0.1 ml) and a culture of mithicillin-resistant Staphylococcus aureus. The samples were studied in pure form, as well as after mixing with QD solution in equal proportions at time intervals of 1 min., 5 min., 10 min., 30 min., 60 and 120 min. respectively, to assess the characteristics of pharmacodynamics. The criterion for the clinical activity of the samples was the determination of zones of growth inhibition using the disc diffusion method.

Results. During the study, it was found that QDs freely penetrate the cell membrane of a bacterial cell; the first signs of cell destruction with the release of its contents begin to be visualized after 30 minutes of observation; the subsequent dynamics of cell destruction is accompanied by a generalized release of contents into the intercellular space, a change in their shape and volume within 60–120 minutes, which indicates a bactericidal effect.

Conclusion. The results obtained demonstrate the promise of further research aimed at studying the technology of combined (conjugated) use of QDs with topical anti-infective agents to increase their anti-infective activity, reduce the risk of selection of strains with multi-drug resistance and the prospect of reducing healthcare costs.

Full Text

Restricted Access

About the authors

V. O. Ponomarev

Yekaterinburg Center of the Interbranch Scientific and Technical Complex “Eye Microsurgery”

Author for correspondence.
Email: Ponomarev-mntk@mail.ru
ORCID iD: 0000-0002-2353-9610

Cand. Sci. (Med.), Deputy General Director for Scientific and Clinical Work

Russian Federation, Yekaterinburg

V. V. Omelyanovsky

Center for Expertise and Quality Control of Medical Care

Email: Ponomarev-mntk@mail.ru
ORCID iD: 0000-0003-1581-0703
Russian Federation, Moscow

References

  1. Algammal A.M., Mabrok M., Sivaramasamy E., et al. Emerging MDR-Pseudomonas aeruginosa in fish commonly harbor oprL and toxA virulence genes and blaTEM, blaCTX-M, and tetA antibiotic-resistance genes. Sci Rep. 2020;10:15961. doi: 10.1038/s41598-020-72264-4.
  2. Al-Kadmy I.M., Ibrahim S.A., Al-Saryi N., et al. Prevalence of genes involved in colistin resistance in Acinetobacter baumannii: First report from Iraq. Microb Drug Resist. 2020;26:616–22. doi: 10.1089/mdr.2019.0243.
  3. CDC. Antimicrobial (AR) Threats Report. Available online: https://www.cdc.gov/drugresistance/biggest-threats.html (accessed on 1 December 2022).
  4. Nageeb W.M., Hetta H.F. The predictive potential of different molecular markers linked to amikacin susceptibility phenotypes in Pseudomonas aeruginosa. PLoS ONE 2022;17:e0267396. doi: 10.1371/journal.pone.0267396.
  5. Algammal A.M., Alfifi K.J., Mabrok M., et al. Newly Emerging MDR B. cereus in Mugil seheli as the First Report Commonly Harbor nhe, hbl, cytK, and pc-plc Virulence Genes and bla1, bla2, tetA, and ermA Resistance Genes. Infect. Drug Resist. 2022;15:2167–85. Doi:10.2147/ IDR.S365254.
  6. Hamad A.A., Sharaf M., Hamza M., et al. Investigation of the Bacterial Contamination and Antibiotic Susceptibility Profile of Bacteria Isolated from Bottled Drinking Water. Microbiol Spectr. 2022;10:e0151621. doi: 10.1128/spectrum.01516-21.
  7. Algammal A.M., Abo Hashem M.E., Alfifi K.J., et al. Sequence Analysis, Antibiogram Profile, Virulence and Antibiotic Resistance Genes of XDR and MDR Gallibacterium anatis Isolated from Layer Chickens in Egypt. Infect. Drug Resist. 2022;15:4321–34. doi: 10.2147/IDR.S377797.
  8. Meshaal A.K., Hetta H.F., Yahia R., et al. In Vitro Antimicrobial Activity of Medicinal Plant Extracts against Some Bacterial Pathogens Isolated from Raw and Processed Meat. Life 2021;11:1178. doi: 10.3390/life11111178.
  9. Michael C.A., Dominey Howes D., Labbate M. The antibiotic resistance cri sis: causes, consequences, and management. Front Public Health. 2014;2:145. doi: 10.3389/fpubh.2014.0014548.
  10. Piddock L.J. The crisis of no new antibiotics – what is the way forward? Lancet Infect Dis. 2012;12(3):249–53. doi: 10.1016/S1473 3099(11)70316 449.
  11. Lushniak B.D. Antibiotic resistance: a public health crisis. Public Health Rep. 2014;129(4):314–16. doi: 10.1177/003335491412900402.
  12. Khalil M.A., Ahmed F.A., Elkhateeb A.F., et al. Virulence characteristics of biofilm-forming acinetobacter baumannii in clinical isolates using a Galleria Mellonella Model. Microorganisms 2021;9:2365. doi: 10.3390/microorganisms9112365.
  13. Algammal A.M., Hetta H.F., Elkelish A., et al. Methicillin-Resistant Staphylococcus aureus (MRSA): One health perspective approach to the bacterium epidemiology, virulence factors, antibiotic-resistance, and zoonotic impact. Infect Drug Resist. 2020;13:3255. doi: 10.2147/IDR.S272733.
  14. Kareem S.M., Al-Kadmy I.M., Kazaal S.S., et al. Detection of gyra and parc mutations and prevalence of plasmid-mediated quinolone resistance genes in Klebsiella pneumoniae. Infect. Drug Resist. 2021;14:555. doi: 10.2147/IDR.S275852.
  15. Abd El-Baky R.M., Masoud S.M., Mohamed D.S., et al. Prevalence and some possible mechanisms of colistin resistance among multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa. Infect. Drug Resist. 2020;13:323. doi: 10.2147/IDR.S238811.
  16. Ovung A., Bhattacharyya J. Sulfonamide drugs: Structure, antibacterial property, toxicity, and biophysical interactions. Biophys Rev. 2021:13:259–72. doi: 10.1007/s12551-021-00795-9.
  17. Khalil M.A., Ahmed F.A., Elkhateeb A.F., et al. Virulence characteristics of biofilm-forming acinetobacter baumannii in clinical isolates using a Galleria Mellonella Model. Microorganisms 2021;9:2365. doi: 10.3390/microorganisms9112365.
  18. Courtney C.M., Goodman S.M., Nagy T.A., et al. Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation. Sci Adv. 2017;3(10):1–10. doi: 10.1126/sciadv.1701776.
  19. Courtney C.M., Goodman S.M., McDaniel J.A., et al. Photoexcited quantum dots for killing multidrug-resistant bacteria. Nat Mater. 2016;15:529–534. doi: 10.1038/nmat4542.
  20. Shobha, G., Moses V., Ananda S. Biological synthesis of copper nanoparticles and its impact. Int J Pharm Sci Invent. 2014;3:6–28. doi: 10.3390/app12010141.
  21. Jaworski S., Wierzbicki M., Sawosz E., et al. Graphene oxide-based nanocomposites decorated with silver nanoparticles as an antibacterial agent. Nanoscale Res Lett. 2018;13:116. doi: 10.1186/s11671-018-2533-2.
  22. Mba I.E., Sharndama H.C., Osondu-Chuka, G.O. et al. Immunobiology and nanotherapeutics of severe acute respiratory syndrome 2 (SARS-CoV-2): A current update. Infect. Dis. 2021;53:559–80. doi: 10.1080/23744235.2021.1916071.
  23. Abid S.A., Muneer A.A., Al-Kadmy I.M., et al. Biosensors as a future diagnostic approach for COVID-19. Life Sci. 2021;273:119117. doi: 10.1016/j.lfs.2021.119117.
  24. Mohler J.S., Sim, W., Blaskovich, M.A., et al. Silver bullets: A new lustre on an old antimicrobial agent. Biotechnol. Adv. 2018;36:1391–411. doi: 10.1016/j.biotechadv.2018.05.004.
  25. Merrifield R.C., Stephan C., Lead J.R. Single-particle inductively coupled plasma mass spectroscopy analysis of size and number concentration in mixtures of monometallic and bimetallic (core-shell) nanoparticles. Talanta. 2017;162:130–34. doi: 10.1016/j.talanta. 2016.09.070.
  26. Rajeshkumar S., Bharath L. Mechanism of plant-mediated synthesis of silver nanoparticles–a review on biomolecules involved, characterisation and antibacterial activity. Chem.-Biol Interact. 2017;273:219–27. doi: 10.1016/j.cbi.2017.06.019.
  27. Gupta A., Mumtaz S., Li C.-H., at al. Combatting antibiotic-resistant bacteria using nanomaterials. Chem Soc Rev. 2019;48:415–27. doi: 10.1039/c7cs00748e.
  28. Muthukrishnan L., Chellappa M., Nanda A. Bio-engineering and cellular imaging of silver nanoparticles as weaponry against multidrug resistant human pathogens. J Photochem Photobiol B Biol. 2019;194:119–27. doi: 10.1016/j.jphotobiol.2019.03.021
  29. Wang L., Hu C., Shao L. The antimicrobial activity of nanoparticles: Present situation and prospects for the future. Int J Nanomed. 2017;12:1227. doi: 10.2147/IJN.S121956.
  30. Slavin Y.N., Asnis J., Hafeli U.O., et al. Metal nanoparticles: Understanding the mechanisms behind antibacterial activity. J Nanobiotechnol. 2017;15:65. doi: 10.1186/s12951-017-0308-z.
  31. Wang X., Du Y., Fan L, et al. Chitosan-metal complexes as antimicrobial agent: Synthesis, characterization and Structure-activity study. Polym Bull. 2005;55:105–13. doi: 10.1007/s00289-005-0414-1.
  32. NatanM., Banin E. From nano to micro: Using nanotechnology to combat microorganisms and their multidrug resistance. FEMS Microbiol Rev. 2017;41:302–22. doi: 10.1093/femsre/fux003.
  33. Golkar Z., Bagazra O., Pace D.G. Bacteriophage therapy: a potential solution for the antibiotic resistance crisis. J Infect Dev Ctries. 2014;8(2):129–36. doi: 10.3855/jidc.3573.
  34. Gould I.M., Bal A.M. New antibiotic agents in the pipeline and how they can overcome microbial resistance. Virulence. 2013;4(2):185–91. doi: 10.4161/viru.22507.
  35. Viswanathan V.K. Off-label abuse of antibiotics by bacteria. Gut Microbes. 2014;5(1):3–4. doi: 10.4161/gmic.28027.
  36. Ragheb M.N., Thomason M.K., Hsu C., et al. Inhibiting the Evolution of Antibiotic Resistance. Mol Cell. 2019;73(1):157–65.e5. doi: 10.1016/j.molcel.2018.10.015.
  37. Prasetyoputri A., Jarrad A.M., Cooper M.A., et al. The Eagle Effect and Antibiotic-Induced Persistence: Two Sides of the Same Coin? Trends Microbiol. 2019;27(4):339–54. doi: 10.1016/j.tim.2018.10.007.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Pharmacodynamic interaction of CT with MRSA culture

Download (679KB)
3. Fig. 2. Dynamics of ZZR change when mixing native vancomycin/lefloxacin solution with 0.001%/0.1 ml InP/ZnSe/ZnS CT solution in equal volume ratios

Download (56KB)

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies