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JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range

Phage therapy represents a possible treatment option to cure infections caused by multidrug-resistant bacteria, including methicillin and vancomycin-resistant Staphylococcus aureus, to which most antibiotics have become ineffective. In the present study, we report the isolation and complete characte...

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Autores principales: Feng, Tingting, Leptihn, Sebastian, Dong, Ke, Loh, Belinda, Zhang, Yan, Stefan, Melanie I., Li, Mingyue, Guo, Xiaokui, Cui, Zelin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100676/
https://www.ncbi.nlm.nih.gov/pubmed/33967969
http://dx.doi.org/10.3389/fmicb.2021.602902
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author Feng, Tingting
Leptihn, Sebastian
Dong, Ke
Loh, Belinda
Zhang, Yan
Stefan, Melanie I.
Li, Mingyue
Guo, Xiaokui
Cui, Zelin
author_facet Feng, Tingting
Leptihn, Sebastian
Dong, Ke
Loh, Belinda
Zhang, Yan
Stefan, Melanie I.
Li, Mingyue
Guo, Xiaokui
Cui, Zelin
author_sort Feng, Tingting
collection PubMed
description Phage therapy represents a possible treatment option to cure infections caused by multidrug-resistant bacteria, including methicillin and vancomycin-resistant Staphylococcus aureus, to which most antibiotics have become ineffective. In the present study, we report the isolation and complete characterization of a novel phage named JD219 exhibiting a broad host range able to infect 61 of 138 clinical strains of S. aureus tested, which included MRSA strains as well. The phage JD419 exhibits a unique morphology with an elongated capsid and a flexible tail. To evaluate the potential of JD419 to be used as a therapeutic phage, we tested the ability of the phage particles to remain infectious after treatment exceeding physiological pH or temperature. The activity was retained at pH values of 6.0–8.0 and below 50°C. As phages can contain virulence genes, JD419’s complete genome was sequenced. The 45509 bp genome is predicted to contain 65 ORFs, none of which show homology to any known virulence or antibiotic resistance genes. Genome analysis indicates that JD419 is a temperate phage, despite observing rapid replication and lysis of host strains. Following the recent advances in synthetic biology, JD419 can be modified by gene engineering to remove prophage-related genes, preventing potential lysogeny, in order to be deployed as a therapeutic phage.
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spelling pubmed-81006762021-05-07 JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range Feng, Tingting Leptihn, Sebastian Dong, Ke Loh, Belinda Zhang, Yan Stefan, Melanie I. Li, Mingyue Guo, Xiaokui Cui, Zelin Front Microbiol Microbiology Phage therapy represents a possible treatment option to cure infections caused by multidrug-resistant bacteria, including methicillin and vancomycin-resistant Staphylococcus aureus, to which most antibiotics have become ineffective. In the present study, we report the isolation and complete characterization of a novel phage named JD219 exhibiting a broad host range able to infect 61 of 138 clinical strains of S. aureus tested, which included MRSA strains as well. The phage JD419 exhibits a unique morphology with an elongated capsid and a flexible tail. To evaluate the potential of JD419 to be used as a therapeutic phage, we tested the ability of the phage particles to remain infectious after treatment exceeding physiological pH or temperature. The activity was retained at pH values of 6.0–8.0 and below 50°C. As phages can contain virulence genes, JD419’s complete genome was sequenced. The 45509 bp genome is predicted to contain 65 ORFs, none of which show homology to any known virulence or antibiotic resistance genes. Genome analysis indicates that JD419 is a temperate phage, despite observing rapid replication and lysis of host strains. Following the recent advances in synthetic biology, JD419 can be modified by gene engineering to remove prophage-related genes, preventing potential lysogeny, in order to be deployed as a therapeutic phage. Frontiers Media S.A. 2021-04-22 /pmc/articles/PMC8100676/ /pubmed/33967969 http://dx.doi.org/10.3389/fmicb.2021.602902 Text en Copyright © 2021 Feng, Leptihn, Dong, Loh, Zhang, Stefan, Li, Guo and Cui. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Feng, Tingting
Leptihn, Sebastian
Dong, Ke
Loh, Belinda
Zhang, Yan
Stefan, Melanie I.
Li, Mingyue
Guo, Xiaokui
Cui, Zelin
JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range
title JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range
title_full JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range
title_fullStr JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range
title_full_unstemmed JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range
title_short JD419, a Staphylococcus aureus Phage With a Unique Morphology and Broad Host Range
title_sort jd419, a staphylococcus aureus phage with a unique morphology and broad host range
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100676/
https://www.ncbi.nlm.nih.gov/pubmed/33967969
http://dx.doi.org/10.3389/fmicb.2021.602902
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