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Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo

Rational: Salmonella Enteritidis (S. Enteritidis) is a globally significant zoonotic foodborne pathogen which has led to large numbers of deaths in humans and caused economic losses in animal husbandry. S. Enteritidis invades host cells and survives within the cells, causing resistance to antibiotic...

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Autores principales: Shi, Shourong, Wu, Shu, Shen, Yiru, Zhang, Shan, Xiao, Yunqi, He, Xi, Gong, Jiansen, Farnell, Yuhua, Tang, Yan, Huang, Yixin, Gao, Lizeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299686/
https://www.ncbi.nlm.nih.gov/pubmed/30613289
http://dx.doi.org/10.7150/thno.29303
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author Shi, Shourong
Wu, Shu
Shen, Yiru
Zhang, Shan
Xiao, Yunqi
He, Xi
Gong, Jiansen
Farnell, Yuhua
Tang, Yan
Huang, Yixin
Gao, Lizeng
author_facet Shi, Shourong
Wu, Shu
Shen, Yiru
Zhang, Shan
Xiao, Yunqi
He, Xi
Gong, Jiansen
Farnell, Yuhua
Tang, Yan
Huang, Yixin
Gao, Lizeng
author_sort Shi, Shourong
collection PubMed
description Rational: Salmonella Enteritidis (S. Enteritidis) is a globally significant zoonotic foodborne pathogen which has led to large numbers of deaths in humans and caused economic losses in animal husbandry. S. Enteritidis invades host cells and survives within the cells, causing resistance to antibiotic treatment. Effective methods of elimination and eradication of intracellular S. Enteritidis are still very limited. Here we evaluated whether a new intracellular antibacterial strategy using iron oxide nanozymes (IONzymes) exerted highly antibacterial efficacy via its intrinsic peroxidase-like activity in vitro and in vivo. Methods: The antibacterial activities of IONzymes against planktonic S. Enteritidis, intracellular S. Enteritidis in Leghorn Male Hepatoma-derived cells (LMH), and liver from specific pathogen free (SPF) chicks were investigated by spread-plate colony count method and cell viability assay. Changes in levels of microtubule-associated protein light chain 3 (LC3), a widely used marker for autophagosomes, were analyzed by immunoblotting, immunofluorescence, and electron microscopy. Reactive oxygen species (ROS) production was also assessed in vitro. High-throughput RNA sequencing was used to investigate the effects of IONzymes on liver transcriptome of S. Enteritidis-infected chicks. Results: We demonstrated that IONzymes had high biocompatibility with cultured LMH cells and chickens, which significantly inhibited intracellular S. Enteritidis survival in vitro and in vivo. In addition, co-localization of IONzymes with S. Enteritidis were observed in autophagic vacuoles of LMH cells and liver of chickens infected by S. Enteritidis, indicating that IONzymes mediated antibacterial reaction of S. Enteritidis with autophagic pathway. We found ROS level was significantly increased in infected LMH cells treated with IONzymes, which might enhance the autophagic elimination of intracellular S. Enteritidis. Moreover, orally administered IONzymes decreased S. Enteritidis organ invasion of the liver and prevented pathological lesions in a chicken-infection model. Non-target transcriptomic profiling also discovered IONzymes could change hepatic oxidation-reduction and autophagy related gene expressions in the S. Enteritidis infected chickens. Conclusion: These data suggest that IONzymes can increase ROS levels to promote the antibacterial effects of acid autophagic vacuoles, and thus suppress the establishment and survival of invading intracellular S. Enteritidis. As a result, IONzymes may be a novel alternative to current antibiotics for the control of intractable S. Enteritidis infections.
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spelling pubmed-62996862019-01-04 Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo Shi, Shourong Wu, Shu Shen, Yiru Zhang, Shan Xiao, Yunqi He, Xi Gong, Jiansen Farnell, Yuhua Tang, Yan Huang, Yixin Gao, Lizeng Theranostics Research Paper Rational: Salmonella Enteritidis (S. Enteritidis) is a globally significant zoonotic foodborne pathogen which has led to large numbers of deaths in humans and caused economic losses in animal husbandry. S. Enteritidis invades host cells and survives within the cells, causing resistance to antibiotic treatment. Effective methods of elimination and eradication of intracellular S. Enteritidis are still very limited. Here we evaluated whether a new intracellular antibacterial strategy using iron oxide nanozymes (IONzymes) exerted highly antibacterial efficacy via its intrinsic peroxidase-like activity in vitro and in vivo. Methods: The antibacterial activities of IONzymes against planktonic S. Enteritidis, intracellular S. Enteritidis in Leghorn Male Hepatoma-derived cells (LMH), and liver from specific pathogen free (SPF) chicks were investigated by spread-plate colony count method and cell viability assay. Changes in levels of microtubule-associated protein light chain 3 (LC3), a widely used marker for autophagosomes, were analyzed by immunoblotting, immunofluorescence, and electron microscopy. Reactive oxygen species (ROS) production was also assessed in vitro. High-throughput RNA sequencing was used to investigate the effects of IONzymes on liver transcriptome of S. Enteritidis-infected chicks. Results: We demonstrated that IONzymes had high biocompatibility with cultured LMH cells and chickens, which significantly inhibited intracellular S. Enteritidis survival in vitro and in vivo. In addition, co-localization of IONzymes with S. Enteritidis were observed in autophagic vacuoles of LMH cells and liver of chickens infected by S. Enteritidis, indicating that IONzymes mediated antibacterial reaction of S. Enteritidis with autophagic pathway. We found ROS level was significantly increased in infected LMH cells treated with IONzymes, which might enhance the autophagic elimination of intracellular S. Enteritidis. Moreover, orally administered IONzymes decreased S. Enteritidis organ invasion of the liver and prevented pathological lesions in a chicken-infection model. Non-target transcriptomic profiling also discovered IONzymes could change hepatic oxidation-reduction and autophagy related gene expressions in the S. Enteritidis infected chickens. Conclusion: These data suggest that IONzymes can increase ROS levels to promote the antibacterial effects of acid autophagic vacuoles, and thus suppress the establishment and survival of invading intracellular S. Enteritidis. As a result, IONzymes may be a novel alternative to current antibiotics for the control of intractable S. Enteritidis infections. Ivyspring International Publisher 2018-11-29 /pmc/articles/PMC6299686/ /pubmed/30613289 http://dx.doi.org/10.7150/thno.29303 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Shi, Shourong
Wu, Shu
Shen, Yiru
Zhang, Shan
Xiao, Yunqi
He, Xi
Gong, Jiansen
Farnell, Yuhua
Tang, Yan
Huang, Yixin
Gao, Lizeng
Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo
title Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo
title_full Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo
title_fullStr Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo
title_full_unstemmed Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo
title_short Iron oxide nanozyme suppresses intracellular Salmonella Enteritidis growth and alleviates infection in vivo
title_sort iron oxide nanozyme suppresses intracellular salmonella enteritidis growth and alleviates infection in vivo
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299686/
https://www.ncbi.nlm.nih.gov/pubmed/30613289
http://dx.doi.org/10.7150/thno.29303
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