The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome

ABSTRACT Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal ef...

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Autores principales:	Timothy A. Johnson, Torey Looft, Andrew J. Severin, Darrell O. Bayles, Daniel J. Nasko, K. Eric Wommack, Adina Howe, Heather K. Allen
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	agricultural antibiotics carbadox metatranscriptomics prophage induction swine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3d8a07994516454c94ded003c5252937
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spelling	oai:doaj.org-article:3d8a07994516454c94ded003c52529372021-11-15T15:51:44ZThe In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome10.1128/mBio.00709-172150-7511https://doaj.org/article/3d8a07994516454c94ded003c52529372017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00709-17https://doaj.org/toc/2150-7511ABSTRACT Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66) related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1), suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ≤0.07), suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration. IMPORTANCE FDA regulations on agricultural antibiotic use have focused on antibiotics that are important for human medicine. Carbadox is an antibiotic not used in humans but frequently used on U.S. pig farms. It is important to study possible side effects of carbadox use because it has been shown to promote bacterial evolution, which could indirectly impact antibiotic resistance in bacteria of clinical importance. Interestingly, the present study shows greater prophage gene expression in feces from carbadox-fed animals than in feces from nonmedicated animals 2 days after the initiation of in-feed carbadox treatment. Importantly, the phage genetic material isolated in this study contained genes that could provide resistance to antibiotics that are important in human medicine, indicating that human-relevant antibiotic resistance genes are mobile between bacteria via phages. This study highlights the collateral effects of antibiotics and demonstrates the need to consider diverse antibiotic effects whenever antibiotics are being used or new regulations are considered.Timothy A. JohnsonTorey LooftAndrew J. SeverinDarrell O. BaylesDaniel J. NaskoK. Eric WommackAdina HoweHeather K. AllenAmerican Society for Microbiologyarticleagricultural antibioticscarbadoxmetatranscriptomicsprophage inductionswineMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	agricultural antibiotics carbadox metatranscriptomics prophage induction swine Microbiology QR1-502
spellingShingle	agricultural antibiotics carbadox metatranscriptomics prophage induction swine Microbiology QR1-502 Timothy A. Johnson Torey Looft Andrew J. Severin Darrell O. Bayles Daniel J. Nasko K. Eric Wommack Adina Howe Heather K. Allen The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome
description	ABSTRACT Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66) related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1), suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ≤0.07), suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration. IMPORTANCE FDA regulations on agricultural antibiotic use have focused on antibiotics that are important for human medicine. Carbadox is an antibiotic not used in humans but frequently used on U.S. pig farms. It is important to study possible side effects of carbadox use because it has been shown to promote bacterial evolution, which could indirectly impact antibiotic resistance in bacteria of clinical importance. Interestingly, the present study shows greater prophage gene expression in feces from carbadox-fed animals than in feces from nonmedicated animals 2 days after the initiation of in-feed carbadox treatment. Importantly, the phage genetic material isolated in this study contained genes that could provide resistance to antibiotics that are important in human medicine, indicating that human-relevant antibiotic resistance genes are mobile between bacteria via phages. This study highlights the collateral effects of antibiotics and demonstrates the need to consider diverse antibiotic effects whenever antibiotics are being used or new regulations are considered.
format	article
author	Timothy A. Johnson Torey Looft Andrew J. Severin Darrell O. Bayles Daniel J. Nasko K. Eric Wommack Adina Howe Heather K. Allen
author_facet	Timothy A. Johnson Torey Looft Andrew J. Severin Darrell O. Bayles Daniel J. Nasko K. Eric Wommack Adina Howe Heather K. Allen
author_sort	Timothy A. Johnson
title	The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome
title_short	The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome
title_full	The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome
title_fullStr	The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome
title_full_unstemmed	The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome
title_sort	in-feed antibiotic carbadox induces phage gene transcription in the swine gut microbiome
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/3d8a07994516454c94ded003c5252937
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The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome

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