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Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses

Currently, control against bovine respiratory disease (BRD) primarily consists of mass administration of an antimicrobial upon arrival to facility, termed “metaphylaxis.” The objective of this study was to determine the influence of six different antimicrobials used as metaphylaxis on the whole bloo...

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Autores principales: Bigelow, Rebecca A., Richeson, John T., McClurg, Molly, Valeris-Chacin, Robert, Morley, Paul S., Funk, Jenna L., Scott, Matthew A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585045/
https://www.ncbi.nlm.nih.gov/pubmed/37869487
http://dx.doi.org/10.3389/fvets.2023.1272940
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author Bigelow, Rebecca A.
Richeson, John T.
McClurg, Molly
Valeris-Chacin, Robert
Morley, Paul S.
Funk, Jenna L.
Scott, Matthew A.
author_facet Bigelow, Rebecca A.
Richeson, John T.
McClurg, Molly
Valeris-Chacin, Robert
Morley, Paul S.
Funk, Jenna L.
Scott, Matthew A.
author_sort Bigelow, Rebecca A.
collection PubMed
description Currently, control against bovine respiratory disease (BRD) primarily consists of mass administration of an antimicrobial upon arrival to facility, termed “metaphylaxis.” The objective of this study was to determine the influence of six different antimicrobials used as metaphylaxis on the whole blood host transcriptome in healthy steers upon and following arrival to the feedlot. One hundred and five steers were stratified by arrival body weight (BW = 247 ± 28 kg) and randomly and equally allocated to one of seven treatments: negative control (NC), ceftiofur (CEFT), enrofloxacin (ENRO), florfenicol (FLOR), oxytetracycline (OXYT), tildipirosin (TILD), or tulathromycin (TULA). On day 0, whole blood samples and BW were collected prior to a one-time administration of the assigned antimicrobial. Blood samples were collected again on days 3, 7, 14, 21, and 56. A subset of cattle (n = 6) per treatment group were selected randomly for RNA sequencing across all time points. Isolated RNA was sequenced (NovaSeq 6,000; ~35 M paired-end reads/sample), where sequenced reads were processed with ARS-UCD1.3 reference-guided assembly (HISAT2/StringTie2). Differential expression analysis comparing treatment groups to NC was performed with glmmSeq (FDR ≤ 0.05) and edgeR (FDR ≤ 0.1). Functional enrichment was performed with KOBAS-i (FDR ≤ 0.05). When compared only to NC, unique differentially expressed genes (DEGs) found within both edgeR and glmmSeq were identified for CEFT (n = 526), ENRO (n = 340), FLOR (n = 56), OXYT (n = 111), TILD (n = 3,001), and TULA (n = 87). At day 3, CEFT, TILD, and OXYT shared multiple functional enrichment pathways related to T-cell receptor signaling and FcεRI-mediated NF-kappa beta (kB) activation. On day 7, Class I major histocompatibility complex (MHC)-mediated antigen presentation pathways were enriched in ENRO and CEFT groups, and CEFT and FLOR had DEGs that affected IL-17 signaling pathways. There were no shared pathways or Gene Ontology (GO) terms among treatments at day 14, but TULA had 19 pathways and eight GO terms enriched related to NF- κβ activation, and interleukin/interferon signaling. Pathways related to cytokine signaling were enriched by TILD on day 21. Our research demonstrates immunomodulation and potential secondary therapeutic mechanisms induced by antimicrobials commonly used for metaphylaxis, providing insight into the beneficial anti-inflammatory properties antimicrobials possess.
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spelling pubmed-105850452023-10-20 Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses Bigelow, Rebecca A. Richeson, John T. McClurg, Molly Valeris-Chacin, Robert Morley, Paul S. Funk, Jenna L. Scott, Matthew A. Front Vet Sci Veterinary Science Currently, control against bovine respiratory disease (BRD) primarily consists of mass administration of an antimicrobial upon arrival to facility, termed “metaphylaxis.” The objective of this study was to determine the influence of six different antimicrobials used as metaphylaxis on the whole blood host transcriptome in healthy steers upon and following arrival to the feedlot. One hundred and five steers were stratified by arrival body weight (BW = 247 ± 28 kg) and randomly and equally allocated to one of seven treatments: negative control (NC), ceftiofur (CEFT), enrofloxacin (ENRO), florfenicol (FLOR), oxytetracycline (OXYT), tildipirosin (TILD), or tulathromycin (TULA). On day 0, whole blood samples and BW were collected prior to a one-time administration of the assigned antimicrobial. Blood samples were collected again on days 3, 7, 14, 21, and 56. A subset of cattle (n = 6) per treatment group were selected randomly for RNA sequencing across all time points. Isolated RNA was sequenced (NovaSeq 6,000; ~35 M paired-end reads/sample), where sequenced reads were processed with ARS-UCD1.3 reference-guided assembly (HISAT2/StringTie2). Differential expression analysis comparing treatment groups to NC was performed with glmmSeq (FDR ≤ 0.05) and edgeR (FDR ≤ 0.1). Functional enrichment was performed with KOBAS-i (FDR ≤ 0.05). When compared only to NC, unique differentially expressed genes (DEGs) found within both edgeR and glmmSeq were identified for CEFT (n = 526), ENRO (n = 340), FLOR (n = 56), OXYT (n = 111), TILD (n = 3,001), and TULA (n = 87). At day 3, CEFT, TILD, and OXYT shared multiple functional enrichment pathways related to T-cell receptor signaling and FcεRI-mediated NF-kappa beta (kB) activation. On day 7, Class I major histocompatibility complex (MHC)-mediated antigen presentation pathways were enriched in ENRO and CEFT groups, and CEFT and FLOR had DEGs that affected IL-17 signaling pathways. There were no shared pathways or Gene Ontology (GO) terms among treatments at day 14, but TULA had 19 pathways and eight GO terms enriched related to NF- κβ activation, and interleukin/interferon signaling. Pathways related to cytokine signaling were enriched by TILD on day 21. Our research demonstrates immunomodulation and potential secondary therapeutic mechanisms induced by antimicrobials commonly used for metaphylaxis, providing insight into the beneficial anti-inflammatory properties antimicrobials possess. Frontiers Media S.A. 2023-10-05 /pmc/articles/PMC10585045/ /pubmed/37869487 http://dx.doi.org/10.3389/fvets.2023.1272940 Text en Copyright © 2023 Bigelow, Richeson, McClurg, Valeris-Chacin, Morley, Funk and Scott. 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 Veterinary Science
Bigelow, Rebecca A.
Richeson, John T.
McClurg, Molly
Valeris-Chacin, Robert
Morley, Paul S.
Funk, Jenna L.
Scott, Matthew A.
Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses
title Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses
title_full Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses
title_fullStr Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses
title_full_unstemmed Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses
title_short Characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses
title_sort characterizing the influence of various antimicrobials used for metaphylaxis against bovine respiratory disease on host transcriptome responses
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585045/
https://www.ncbi.nlm.nih.gov/pubmed/37869487
http://dx.doi.org/10.3389/fvets.2023.1272940
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