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Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability

Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays...

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Autores principales: Zhang, Xiaolin, Jiang, Anmin, Yu, Hao, Xiong, Youyi, Zhou, Guoliang, Qin, Meisong, Dou, Jinfeng, Wang, Jianfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273225/
https://www.ncbi.nlm.nih.gov/pubmed/27801837
http://dx.doi.org/10.3390/molecules21111435
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author Zhang, Xiaolin
Jiang, Anmin
Yu, Hao
Xiong, Youyi
Zhou, Guoliang
Qin, Meisong
Dou, Jinfeng
Wang, Jianfei
author_facet Zhang, Xiaolin
Jiang, Anmin
Yu, Hao
Xiong, Youyi
Zhou, Guoliang
Qin, Meisong
Dou, Jinfeng
Wang, Jianfei
author_sort Zhang, Xiaolin
collection PubMed
description Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.
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spelling pubmed-62732252018-12-28 Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability Zhang, Xiaolin Jiang, Anmin Yu, Hao Xiong, Youyi Zhou, Guoliang Qin, Meisong Dou, Jinfeng Wang, Jianfei Molecules Article Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations. MDPI 2016-10-28 /pmc/articles/PMC6273225/ /pubmed/27801837 http://dx.doi.org/10.3390/molecules21111435 Text en © 2016 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Xiaolin
Jiang, Anmin
Yu, Hao
Xiong, Youyi
Zhou, Guoliang
Qin, Meisong
Dou, Jinfeng
Wang, Jianfei
Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability
title Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability
title_full Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability
title_fullStr Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability
title_full_unstemmed Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability
title_short Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability
title_sort human lysozyme synergistically enhances bactericidal dynamics and lowers the resistant mutant prevention concentration for metronidazole to helicobacter pylori by increasing cell permeability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273225/
https://www.ncbi.nlm.nih.gov/pubmed/27801837
http://dx.doi.org/10.3390/molecules21111435
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