Cargando…
Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles
To prevent the rapidly increasing prevalence of bacterial resistance, it is crucial to discover new antibacterial agents. The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae has been associated with a higher mortality rate in gulf union countries and worldwide. Co...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055515/ https://www.ncbi.nlm.nih.gov/pubmed/36985482 http://dx.doi.org/10.3390/molecules28062510 |
_version_ | 1785015890037702656 |
---|---|
author | Elsayim, Rasha Aloufi, Abeer S. Modafer, Yosra Eltayb, Wafa Ali Alameen, Alaa Alnoor Abdurahim, Samah Awad |
author_facet | Elsayim, Rasha Aloufi, Abeer S. Modafer, Yosra Eltayb, Wafa Ali Alameen, Alaa Alnoor Abdurahim, Samah Awad |
author_sort | Elsayim, Rasha |
collection | PubMed |
description | To prevent the rapidly increasing prevalence of bacterial resistance, it is crucial to discover new antibacterial agents. The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae has been associated with a higher mortality rate in gulf union countries and worldwide. Compared to physical and chemical approaches, green zinc oxide nanoparticle (ZnO-NP) synthesis is thought to be significantly safer and more ecofriendly. The present study used molecular dynamics (MD) to examine how ZnO-NPs interact with porin protein (GLO21), a target of β-lactam antibiotics, and then tested this interaction in vitro by determining the zone of inhibition (IZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC), as well as the alteration of KPC’s cell surface. The nanoparticles produced were characterized by UV-Vis spectroscopy, zetasizer, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). In silico investigation was conducted using a variety of computational techniques, including Autodock Vina for protein and ligand docking and Desmond for MD simulation. The candidate ligands that interact with the GLO21 protein were biosynthesized ZnO-NPs, meropenem, imipenem, and cefepime. Analysis of MD revealed that the ZnO-NPs had the highest log P value (−9.1 kcal/mol), which indicates higher permeability through the bacterial surface, followed by cefepime (−7.9 kcal/mol), meropenem (−7.5 kcal/mol), and imipenem (−6.4 kcal/mol). All tested compounds and ZnO-NPs possess similar binding sites of porin proteins. An MD simulation study showed a stable system for ZnO-NPs and cefepime, as confirmed by RMSD and RMSF values during 100 ns trajectories. The test compounds were further inspected for their intersection with porin in terms of hydrophobic, hydrogen, and ionic levels. In addition, the stability of these bonds were measured by observing the protein–ligand contact within 100 ns trajectories. ZnO-NPs showed promising results for fighting KPC, represented in MIC (0.2 mg/mL), MBC (0.5 mg/mL), and ZI (24 mm diameter). To draw the conclusion that ZnO-NP is a potent antibacterial agent and in order to identify potent antibacterial drugs that do not harm human cells, further in vivo studies are required. |
format | Online Article Text |
id | pubmed-10055515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100555152023-03-30 Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles Elsayim, Rasha Aloufi, Abeer S. Modafer, Yosra Eltayb, Wafa Ali Alameen, Alaa Alnoor Abdurahim, Samah Awad Molecules Article To prevent the rapidly increasing prevalence of bacterial resistance, it is crucial to discover new antibacterial agents. The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae has been associated with a higher mortality rate in gulf union countries and worldwide. Compared to physical and chemical approaches, green zinc oxide nanoparticle (ZnO-NP) synthesis is thought to be significantly safer and more ecofriendly. The present study used molecular dynamics (MD) to examine how ZnO-NPs interact with porin protein (GLO21), a target of β-lactam antibiotics, and then tested this interaction in vitro by determining the zone of inhibition (IZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC), as well as the alteration of KPC’s cell surface. The nanoparticles produced were characterized by UV-Vis spectroscopy, zetasizer, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). In silico investigation was conducted using a variety of computational techniques, including Autodock Vina for protein and ligand docking and Desmond for MD simulation. The candidate ligands that interact with the GLO21 protein were biosynthesized ZnO-NPs, meropenem, imipenem, and cefepime. Analysis of MD revealed that the ZnO-NPs had the highest log P value (−9.1 kcal/mol), which indicates higher permeability through the bacterial surface, followed by cefepime (−7.9 kcal/mol), meropenem (−7.5 kcal/mol), and imipenem (−6.4 kcal/mol). All tested compounds and ZnO-NPs possess similar binding sites of porin proteins. An MD simulation study showed a stable system for ZnO-NPs and cefepime, as confirmed by RMSD and RMSF values during 100 ns trajectories. The test compounds were further inspected for their intersection with porin in terms of hydrophobic, hydrogen, and ionic levels. In addition, the stability of these bonds were measured by observing the protein–ligand contact within 100 ns trajectories. ZnO-NPs showed promising results for fighting KPC, represented in MIC (0.2 mg/mL), MBC (0.5 mg/mL), and ZI (24 mm diameter). To draw the conclusion that ZnO-NP is a potent antibacterial agent and in order to identify potent antibacterial drugs that do not harm human cells, further in vivo studies are required. MDPI 2023-03-09 /pmc/articles/PMC10055515/ /pubmed/36985482 http://dx.doi.org/10.3390/molecules28062510 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Elsayim, Rasha Aloufi, Abeer S. Modafer, Yosra Eltayb, Wafa Ali Alameen, Alaa Alnoor Abdurahim, Samah Awad Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles |
title | Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles |
title_full | Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles |
title_fullStr | Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles |
title_full_unstemmed | Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles |
title_short | Molecular Dynamic Analysis of Carbapenem-Resistant Klebsiella pneumonia’s Porin Proteins with Beta Lactam Antibiotics and Zinc Oxide Nanoparticles |
title_sort | molecular dynamic analysis of carbapenem-resistant klebsiella pneumonia’s porin proteins with beta lactam antibiotics and zinc oxide nanoparticles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055515/ https://www.ncbi.nlm.nih.gov/pubmed/36985482 http://dx.doi.org/10.3390/molecules28062510 |
work_keys_str_mv | AT elsayimrasha moleculardynamicanalysisofcarbapenemresistantklebsiellapneumoniasporinproteinswithbetalactamantibioticsandzincoxidenanoparticles AT aloufiabeers moleculardynamicanalysisofcarbapenemresistantklebsiellapneumoniasporinproteinswithbetalactamantibioticsandzincoxidenanoparticles AT modaferyosra moleculardynamicanalysisofcarbapenemresistantklebsiellapneumoniasporinproteinswithbetalactamantibioticsandzincoxidenanoparticles AT eltaybwafaali moleculardynamicanalysisofcarbapenemresistantklebsiellapneumoniasporinproteinswithbetalactamantibioticsandzincoxidenanoparticles AT alameenalaaalnoor moleculardynamicanalysisofcarbapenemresistantklebsiellapneumoniasporinproteinswithbetalactamantibioticsandzincoxidenanoparticles AT abdurahimsamahawad moleculardynamicanalysisofcarbapenemresistantklebsiellapneumoniasporinproteinswithbetalactamantibioticsandzincoxidenanoparticles |