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Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes

BACKGROUND: Antibiotic resistance developed by bacteria is a significant threat to global health. Antibiotic resistance genes (ARGs) spread across different bacterial populations through multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages. ARGs carried by bac...

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Autores principales: Moon, Kira, Jeon, Jeong Ho, Kang, Ilnam, Park, Kwang Seung, Lee, Kihyun, Cha, Chang-Jun, Lee, Sang Hee, Cho, Jang-Cheon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265639/
https://www.ncbi.nlm.nih.gov/pubmed/32482165
http://dx.doi.org/10.1186/s40168-020-00863-4
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author Moon, Kira
Jeon, Jeong Ho
Kang, Ilnam
Park, Kwang Seung
Lee, Kihyun
Cha, Chang-Jun
Lee, Sang Hee
Cho, Jang-Cheon
author_facet Moon, Kira
Jeon, Jeong Ho
Kang, Ilnam
Park, Kwang Seung
Lee, Kihyun
Cha, Chang-Jun
Lee, Sang Hee
Cho, Jang-Cheon
author_sort Moon, Kira
collection PubMed
description BACKGROUND: Antibiotic resistance developed by bacteria is a significant threat to global health. Antibiotic resistance genes (ARGs) spread across different bacterial populations through multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages. ARGs carried by bacteriophages are considered especially threatening due to their prolonged persistence in the environment, fast replication rates, and ability to infect diverse bacterial hosts. Several studies employing qPCR and viral metagenomics have shown that viral fraction and viral sequence reads in clinical and environmental samples carry many ARGs. However, only a few ARGs have been found in viral contigs assembled from metagenome reads, with most of these genes lacking effective antibiotic resistance phenotypes. Owing to the wide application of viral metagenomics, nevertheless, different classes of ARGs are being continuously found in viral metagenomes acquired from diverse environments. As such, the presence and functionality of ARGs encoded by bacteriophages remain up for debate. RESULTS: We evaluated ARGs excavated from viral contigs recovered from urban surface water viral metagenome data. In virome reads and contigs, diverse ARGs, including polymyxin resistance genes, multidrug efflux proteins, and β-lactamases, were identified. In particular, when a lenient threshold of e value of ≤ 1 × e(−5) and query coverage of ≥ 60% were employed in the Resfams database, the novel β-lactamases bla(HRV-1) and bla(HRVM-1) were found. These genes had unique sequences, forming distinct clades of class A and subclass B3 β-lactamases, respectively. Minimum inhibitory concentration analyses for E. coli strains harboring bla(HRV-1) and bla(HRVM-1) and catalytic kinetics of purified HRV-1 and HRVM-1 showed reduced susceptibility to penicillin, narrow- and extended-spectrum cephalosporins, and carbapenems. These genes were also found in bacterial metagenomes, indicating that they were harbored by actively infecting phages. CONCLUSION: Our results showed that viruses in the environment carry as-yet-unreported functional ARGs, albeit in small quantities. We thereby suggest that environmental bacteriophages could be reservoirs of widely variable, unknown ARGs that could be disseminated via virus-host interactions.
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spelling pubmed-72656392020-06-07 Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes Moon, Kira Jeon, Jeong Ho Kang, Ilnam Park, Kwang Seung Lee, Kihyun Cha, Chang-Jun Lee, Sang Hee Cho, Jang-Cheon Microbiome Research BACKGROUND: Antibiotic resistance developed by bacteria is a significant threat to global health. Antibiotic resistance genes (ARGs) spread across different bacterial populations through multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages. ARGs carried by bacteriophages are considered especially threatening due to their prolonged persistence in the environment, fast replication rates, and ability to infect diverse bacterial hosts. Several studies employing qPCR and viral metagenomics have shown that viral fraction and viral sequence reads in clinical and environmental samples carry many ARGs. However, only a few ARGs have been found in viral contigs assembled from metagenome reads, with most of these genes lacking effective antibiotic resistance phenotypes. Owing to the wide application of viral metagenomics, nevertheless, different classes of ARGs are being continuously found in viral metagenomes acquired from diverse environments. As such, the presence and functionality of ARGs encoded by bacteriophages remain up for debate. RESULTS: We evaluated ARGs excavated from viral contigs recovered from urban surface water viral metagenome data. In virome reads and contigs, diverse ARGs, including polymyxin resistance genes, multidrug efflux proteins, and β-lactamases, were identified. In particular, when a lenient threshold of e value of ≤ 1 × e(−5) and query coverage of ≥ 60% were employed in the Resfams database, the novel β-lactamases bla(HRV-1) and bla(HRVM-1) were found. These genes had unique sequences, forming distinct clades of class A and subclass B3 β-lactamases, respectively. Minimum inhibitory concentration analyses for E. coli strains harboring bla(HRV-1) and bla(HRVM-1) and catalytic kinetics of purified HRV-1 and HRVM-1 showed reduced susceptibility to penicillin, narrow- and extended-spectrum cephalosporins, and carbapenems. These genes were also found in bacterial metagenomes, indicating that they were harbored by actively infecting phages. CONCLUSION: Our results showed that viruses in the environment carry as-yet-unreported functional ARGs, albeit in small quantities. We thereby suggest that environmental bacteriophages could be reservoirs of widely variable, unknown ARGs that could be disseminated via virus-host interactions. BioMed Central 2020-06-01 /pmc/articles/PMC7265639/ /pubmed/32482165 http://dx.doi.org/10.1186/s40168-020-00863-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Moon, Kira
Jeon, Jeong Ho
Kang, Ilnam
Park, Kwang Seung
Lee, Kihyun
Cha, Chang-Jun
Lee, Sang Hee
Cho, Jang-Cheon
Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
title Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
title_full Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
title_fullStr Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
title_full_unstemmed Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
title_short Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
title_sort freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265639/
https://www.ncbi.nlm.nih.gov/pubmed/32482165
http://dx.doi.org/10.1186/s40168-020-00863-4
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