Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis

Objectives: The aim of this study was to examine how the concentrated delivery of less effective antibiotics, such as the β-lactam penicillin G, by linkage to nanoparticles (NPs), could influence the killing efficiency against various pathogenic bacteria, including methicillin-resistant Staphylococc...

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Main Authors: Amjed Alabresm, Yung Pin Chen, Savannah Wichter-Chandler, Jamie Lead, Brian C. Benicewicz, Alan W. Decho
Format: Article
Language:English
Published: Elsevier 2020-09-01
Series:Journal of Global Antimicrobial Resistance
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213716520301685
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author Amjed Alabresm
Yung Pin Chen
Savannah Wichter-Chandler
Jamie Lead
Brian C. Benicewicz
Alan W. Decho
author_facet Amjed Alabresm
Yung Pin Chen
Savannah Wichter-Chandler
Jamie Lead
Brian C. Benicewicz
Alan W. Decho
author_sort Amjed Alabresm
collection DOAJ
description Objectives: The aim of this study was to examine how the concentrated delivery of less effective antibiotics, such as the β-lactam penicillin G, by linkage to nanoparticles (NPs), could influence the killing efficiency against various pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug resistant (MDR) strains. Methods: The β-lactam antibiotic penicillin G (PenG) was passively sorbed to fluorescent polystyrene NPs (20 nm) that were surface-functionalized with carboxylic acid (COO−-NPs) or sulfate groups (SO4−-NPs) to form a PenG-NP complex. Antimicrobial activities of PenG-NPs were evaluated against Gram-negative and Gram-positive bacteria, including antibiotic resistant strains. Disc diffusion, microdilution assays and live/dead staining were performed for antibacterial assessments. Results: The results showed that bactericidal activities of PenG-NP complexes were statistically significantly (P < 0.05) enhanced against Gram-negative and Gram-positive strains, including MRSA and MDR strains. Fluorescence imaging verified that NPs comigrated with antibiotics throughout clear zones of MIC agar plate assays. The increased bactericidal abilities of NP-linked antibiotics are hypothesized to result from the greatly increased densities of antibiotic delivered by each NP to a given bacterial cell (compared with solution concentrations of antibiotic), which overwhelms the bacterial resistance mechanism(s). Conclusions: As a whole, PenG-NP complexation demonstrated a remarkable activity against different pathogenic bacteria, including MRSA and MDR strains. We term this the ‘grenade hypothesis’. Further testing and development of this approach will provide validation of its potential usefulness for controlling antibiotic-resistant bacterial infections.
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spelling doaj.art-ab79910c96ce4fdaa66a0a86dfd7f47a2022-12-21T18:59:25ZengElsevierJournal of Global Antimicrobial Resistance2213-71652020-09-0122811817Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesisAmjed Alabresm0Yung Pin Chen1Savannah Wichter-Chandler2Jamie Lead3Brian C. Benicewicz4Alan W. Decho5Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States; Center for Environmental Nanoscience and Risk (CENR), University of South Carolina, Columbia, SC, United States; Department of Biological Development of Shatt Al-Arab &amp; N. Arabian Gulf, Marine Science Centre, University of Basrah, Basrah, IraqDepartment of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United StatesDepartment of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United StatesDepartment of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States; Center for Environmental Nanoscience and Risk (CENR), University of South Carolina, Columbia, SC, United StatesDepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, United StatesDepartment of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States; Corresponding author at: Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States.Objectives: The aim of this study was to examine how the concentrated delivery of less effective antibiotics, such as the β-lactam penicillin G, by linkage to nanoparticles (NPs), could influence the killing efficiency against various pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug resistant (MDR) strains. Methods: The β-lactam antibiotic penicillin G (PenG) was passively sorbed to fluorescent polystyrene NPs (20 nm) that were surface-functionalized with carboxylic acid (COO−-NPs) or sulfate groups (SO4−-NPs) to form a PenG-NP complex. Antimicrobial activities of PenG-NPs were evaluated against Gram-negative and Gram-positive bacteria, including antibiotic resistant strains. Disc diffusion, microdilution assays and live/dead staining were performed for antibacterial assessments. Results: The results showed that bactericidal activities of PenG-NP complexes were statistically significantly (P < 0.05) enhanced against Gram-negative and Gram-positive strains, including MRSA and MDR strains. Fluorescence imaging verified that NPs comigrated with antibiotics throughout clear zones of MIC agar plate assays. The increased bactericidal abilities of NP-linked antibiotics are hypothesized to result from the greatly increased densities of antibiotic delivered by each NP to a given bacterial cell (compared with solution concentrations of antibiotic), which overwhelms the bacterial resistance mechanism(s). Conclusions: As a whole, PenG-NP complexation demonstrated a remarkable activity against different pathogenic bacteria, including MRSA and MDR strains. We term this the ‘grenade hypothesis’. Further testing and development of this approach will provide validation of its potential usefulness for controlling antibiotic-resistant bacterial infections.http://www.sciencedirect.com/science/article/pii/S2213716520301685AntibioticNanoparticleAntibiotic-resistancePenicillin-GMRSAMDR
spellingShingle Amjed Alabresm
Yung Pin Chen
Savannah Wichter-Chandler
Jamie Lead
Brian C. Benicewicz
Alan W. Decho
Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis
Journal of Global Antimicrobial Resistance
Antibiotic
Nanoparticle
Antibiotic-resistance
Penicillin-G
MRSA
MDR
title Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis
title_full Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis
title_fullStr Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis
title_full_unstemmed Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis
title_short Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: The grenade hypothesis
title_sort nanoparticles as antibiotic delivery vehicles advs overcome resistance by mrsa and other mdr bacterial pathogens the grenade hypothesis
topic Antibiotic
Nanoparticle
Antibiotic-resistance
Penicillin-G
MRSA
MDR
url http://www.sciencedirect.com/science/article/pii/S2213716520301685
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