Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis

<i>Pseudomonas aeruginosa</i> is an opportunistic gram-negative human pathogen that causes a wide range of infections, including nosocomial infections. Aside from the intrinsic and acquired antimicrobial resistance against many classes of antibiotics, <i>P. aeruginosa</i> can...

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Main Authors: Mohamed El-Telbany, Alzhraa Ali Mohamed, Galal Yahya, Aliaa Abdelghafar, Mahmoud Saad Abdel-Halim, Sameh Saber, Mohamed A. Alfaleh, Asmaa H. Mohamed, Fatma Abdelrahman, Hoda A. Fathey, Gehad H. Ali, Mohamed Abdel-Haleem
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/11/10/1374
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author Mohamed El-Telbany
Alzhraa Ali Mohamed
Galal Yahya
Aliaa Abdelghafar
Mahmoud Saad Abdel-Halim
Sameh Saber
Mohamed A. Alfaleh
Asmaa H. Mohamed
Fatma Abdelrahman
Hoda A. Fathey
Gehad H. Ali
Mohamed Abdel-Haleem
author_facet Mohamed El-Telbany
Alzhraa Ali Mohamed
Galal Yahya
Aliaa Abdelghafar
Mahmoud Saad Abdel-Halim
Sameh Saber
Mohamed A. Alfaleh
Asmaa H. Mohamed
Fatma Abdelrahman
Hoda A. Fathey
Gehad H. Ali
Mohamed Abdel-Haleem
author_sort Mohamed El-Telbany
collection DOAJ
description <i>Pseudomonas aeruginosa</i> is an opportunistic gram-negative human pathogen that causes a wide range of infections, including nosocomial infections. Aside from the intrinsic and acquired antimicrobial resistance against many classes of antibiotics, <i>P. aeruginosa</i> can produce an extracellular polymeric matrix called “biofilm” that protects bacteria from antibiotics and harmful factors. Biofilm enables <i>P. aeruginosa</i> to develop chronic infections. This study assessed the inhibitory action of ZnO-nanoparticles against biofilms formed by multidrug-resistant <i>P. aeruginosa</i> strains. A collection of 24 clinical strains of <i>P. aeruginosa</i> were tested for their antimicrobial resistance against different antibiotics using the disk diffusion method. The antibiofilm activity of ZnO-NPs was assessed using the microtiter plate biofilm assay. The application of ZnO-NPs dramatically modulated the resistance profile and biofilm activity of <i>P. aeruginosa</i>. The combination of ZnO-NPs and meropenem showed synergistic antipseudomonal activity with lower MICs. The scanning electron microscope (SEM) micrographs revealed complete inhibition of biofilms treated with the meropenem–ZnO-NPs combination. Reduced expression of biofilm regulating genes <i>lasR</i>, <i>pslA,</i> and <i>fliC</i> was detected, reflecting the enhanced antibiofilm effect of ZnO-NPs. In vivo application of this antimicrobial mixture completely cured <i>P. aeruginosa</i>-induced keratitis in rats. Our findings represent a dual enhancement of antibacterial and antibiofilm activity via the use of meropenem–ZnO-NPs combination against carbapenem-resistant <i>P. aeruginosa</i> infections.
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spelling doaj.art-989d18b2a77740e0903439cc5e2955052023-11-23T22:35:23ZengMDPI AGAntibiotics2079-63822022-10-011110137410.3390/antibiotics11101374Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial KeratitisMohamed El-Telbany0Alzhraa Ali Mohamed1Galal Yahya2Aliaa Abdelghafar3Mahmoud Saad Abdel-Halim4Sameh Saber5Mohamed A. Alfaleh6Asmaa H. Mohamed7Fatma Abdelrahman8Hoda A. Fathey9Gehad H. Ali10Mohamed Abdel-Haleem11Microbiology and Botany Department, Faculty of Science, Zagazig University, Zagazig 44519, EgyptMicrobiology and Botany Department, Faculty of Science, Zagazig University, Zagazig 44519, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaMicrobiology and Botany Department, Faculty of Science, Zagazig University, Zagazig 44519, EgyptCenter for Microbiology and Phage Therapy, Zewail City of Science and Technology, Giza 12578, EgyptMicrobiology and Botany Department, Faculty of Science, Zagazig University, Zagazig 44519, EgyptMicrobiology and Botany Department, Faculty of Science, Zagazig University, Zagazig 44519, EgyptMicrobiology and Botany Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt<i>Pseudomonas aeruginosa</i> is an opportunistic gram-negative human pathogen that causes a wide range of infections, including nosocomial infections. Aside from the intrinsic and acquired antimicrobial resistance against many classes of antibiotics, <i>P. aeruginosa</i> can produce an extracellular polymeric matrix called “biofilm” that protects bacteria from antibiotics and harmful factors. Biofilm enables <i>P. aeruginosa</i> to develop chronic infections. This study assessed the inhibitory action of ZnO-nanoparticles against biofilms formed by multidrug-resistant <i>P. aeruginosa</i> strains. A collection of 24 clinical strains of <i>P. aeruginosa</i> were tested for their antimicrobial resistance against different antibiotics using the disk diffusion method. The antibiofilm activity of ZnO-NPs was assessed using the microtiter plate biofilm assay. The application of ZnO-NPs dramatically modulated the resistance profile and biofilm activity of <i>P. aeruginosa</i>. The combination of ZnO-NPs and meropenem showed synergistic antipseudomonal activity with lower MICs. The scanning electron microscope (SEM) micrographs revealed complete inhibition of biofilms treated with the meropenem–ZnO-NPs combination. Reduced expression of biofilm regulating genes <i>lasR</i>, <i>pslA,</i> and <i>fliC</i> was detected, reflecting the enhanced antibiofilm effect of ZnO-NPs. In vivo application of this antimicrobial mixture completely cured <i>P. aeruginosa</i>-induced keratitis in rats. Our findings represent a dual enhancement of antibacterial and antibiofilm activity via the use of meropenem–ZnO-NPs combination against carbapenem-resistant <i>P. aeruginosa</i> infections.https://www.mdpi.com/2079-6382/11/10/1374<i>Pseudomonas aeruginosa</i>biofilmsantimicrobial resistanceZnO-NPsgene expressionmeropenem
spellingShingle Mohamed El-Telbany
Alzhraa Ali Mohamed
Galal Yahya
Aliaa Abdelghafar
Mahmoud Saad Abdel-Halim
Sameh Saber
Mohamed A. Alfaleh
Asmaa H. Mohamed
Fatma Abdelrahman
Hoda A. Fathey
Gehad H. Ali
Mohamed Abdel-Haleem
Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis
Antibiotics
<i>Pseudomonas aeruginosa</i>
biofilms
antimicrobial resistance
ZnO-NPs
gene expression
meropenem
title Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis
title_full Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis
title_fullStr Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis
title_full_unstemmed Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis
title_short Combination of Meropenem and Zinc Oxide Nanoparticles; Antimicrobial Synergism, Exaggerated Antibiofilm Activity, and Efficient Therapeutic Strategy against Bacterial Keratitis
title_sort combination of meropenem and zinc oxide nanoparticles antimicrobial synergism exaggerated antibiofilm activity and efficient therapeutic strategy against bacterial keratitis
topic <i>Pseudomonas aeruginosa</i>
biofilms
antimicrobial resistance
ZnO-NPs
gene expression
meropenem
url https://www.mdpi.com/2079-6382/11/10/1374
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