scholarly journals Comprehensive at-arrival transcriptomic analysis of post-weaned beef cattle uncovers type I interferon and antiviral mechanisms associated with bovine respiratory disease mortality

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250758
Author(s):  
Matthew A. Scott ◽  
Amelia R. Woolums ◽  
Cyprianna E. Swiderski ◽  
Andy D. Perkins ◽  
Bindu Nanduri ◽  
...  

Background Despite decades of extensive research, bovine respiratory disease (BRD) remains the most devastating disease in beef cattle production. Establishing a clinical diagnosis often relies upon visual detection of non-specific signs, leading to low diagnostic accuracy. Thus, post-weaned beef cattle are often metaphylactically administered antimicrobials at facility arrival, which poses concerns regarding antimicrobial stewardship and resistance. Additionally, there is a lack of high-quality research that addresses the gene-by-environment interactions that underlie why some cattle that develop BRD die while others survive. Therefore, it is necessary to decipher the underlying host genomic factors associated with BRD mortality versus survival to help determine BRD risk and severity. Using transcriptomic analysis of at-arrival whole blood samples from cattle that died of BRD, as compared to those that developed signs of BRD but lived (n = 3 DEAD, n = 3 ALIVE), we identified differentially expressed genes (DEGs) and associated pathways in cattle that died of BRD. Additionally, we evaluated unmapped reads, which are often overlooked within transcriptomic experiments. Results 69 DEGs (FDR<0.10) were identified between ALIVE and DEAD cohorts. Several DEGs possess immunological and proinflammatory function and associations with TLR4 and IL6. Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival. Unmapped reads aligned primarily to various ungulate assemblies, but failed to align to viral assemblies. Conclusion This study further revealed increased proinflammatory immunological mechanisms in cattle that develop BRD. DEGs upregulated in DEAD cattle were predominantly involved in innate immune pathways typically associated with antiviral defense, although no viral genes were identified within unmapped reads. Our findings provide genomic targets for further analysis in cattle at highest risk of BRD, suggesting that mechanisms related to type I interferons and antiviral defense may be indicative of viral respiratory disease at arrival and contribute to eventual BRD mortality.

2020 ◽  
Author(s):  
Matthew A. Scott ◽  
Amelia R. Woolums ◽  
Cyprianna E. Swiderski ◽  
Andy D. Perkins ◽  
Bindu Nanduri ◽  
...  

Abstract BackgroundDespite decades of extensive research, bovine respiratory disease (BRD) remains the most devastating disease in beef cattle production. Clinical diagnosis relies upon non-specific signs, which lack sensitivity. Thus, post-weaned beef cattle are often metaphylactically administered antimicrobials at facility arrival, which poses concerns regarding antimicrobial stewardship and resistance. Additionally, there is a lack of high-quality research that addresses the gene-by-environment interactions that underlie why some cattle that develop BRD die while others survive. Therefore, it is necessary to decipher the underlying host genomic factors associated with BRD mortality versus survival to help determine BRD risk and severity. Using transcriptomic analysis of at-arrival whole blood samples from cattle that died of BRD, as compared to those that developed signs of BRD but lived (n = 3 DEAD, n = 3 ALIVE), we identified differentially expressed genes (DEGs) and associated pathways in cattle that died of BRD. Additionally, we evaluated unmapped reads, which are often overlooked within transcriptomic experiments.Results69 DEGs (FDR < 0.10) were identified between ALIVE and DEAD cohorts. Several DEGs possess immunological and proinflammatory function and associations with TLR4 and IL6. Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival. Unmapped reads aligned primarily to various ungulate assemblies, but failed to align to viral assemblies.ConclusionThis study further revealed increased proinflammatory immunological mechanisms in cattle that develop BRD. DEGs upregulated in DEAD cattle were predominantly involved in innate immune pathways typically associated with antiviral defense, although no viral genes were identified within unmapped reads. Our findings provide genomic targets for further analysis in cattle at highest risk of BRD, suggesting that mechanisms related to type I interferons and antiviral defense may be indicative of viral respiratory disease at arrival and contribute to eventual BRD mortality.


2021 ◽  
Author(s):  
Matthew Scott ◽  
Amelia Woolums ◽  
Cyprianna Swiderski ◽  
Alexis Thompson ◽  
Andy Perkins ◽  
...  

Abstract BackgroundTranscriptomics has identified at-arrival differentially expressed genes associated with bovine respiratory disease (BRD) development; however, their use as prediction molecules necessitates further evaluation. Therefore, we aimed to selectively analyze and corroborate at-arrival mRNA expression from multiple independent populations of beef cattle. In a nested case-control study, we evaluated the expression of 56 mRNA molecules from at-arrival blood samples of 234 cattle across seven populations via NanoString nCounter gene expression profiling. Analysis of mRNA was performed with nSolver Advanced Analysis software (p<0.05), comparing cattle groups based on the diagnosis of clinical BRD within 28 days of facility arrival (n=115 Healthy; n=119 BRD); BRD was further stratified for severity based on frequency of treatment and/or mortality (Treated_1, n=89; Treated_2+, n=30). Gene expression homogeneity of variance, receiver operator characteristic (ROC) curve, and decision tree analyses were performed between severity cohorts.ResultsIncreased expression of mRNAs involved in specialized pro-resolving mediator synthesis (ALOX15, HPGD), leukocyte differentiation (LOC100297044, GCSAML, KLF17), and antimicrobial peptide production (CATHL3, GZMB, LTF) were identified in Healthy cattle. BRD cattle possessed increased expression of CFB, and mRNA related to granulocytic processes (DSG1, LRG1, MCF2L) and type-I interferon activity (HERC6, IFI6, ISG15, MX1). Healthy and Treated_1 cattle were similar in terms of gene expression, while Treated_2+ cattle were the most distinct. ROC cutoffs were used to generate an at-arrival treatment decision tree, which classified 90% of Treated_2+ individuals. ConclusionsIncreased expression of complement factor B, pro-inflammatory, and type I interferon-associated mRNA hallmark the at-arrival expression patterns of cattle that develop severe clinical BRD. Here, we corroborate at-arrival mRNA markers identified in previous transcriptome studies and generate a prediction model to be evaluated in future studies. Further research is necessary to evaluate these expression patterns in a prospective manner.


PLoS ONE ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. e0227507 ◽  
Author(s):  
Matthew A. Scott ◽  
Amelia R. Woolums ◽  
Cyprianna E. Swiderski ◽  
Andy D. Perkins ◽  
Bindu Nanduri ◽  
...  

Genomics ◽  
2020 ◽  
Vol 112 (6) ◽  
pp. 3968-3977
Author(s):  
Hui-Zeng Sun ◽  
Vythegi Srithayakumar ◽  
Janelle Jiminez ◽  
Weiwu Jin ◽  
Afshin Hosseini ◽  
...  

2019 ◽  
Vol 66 (3) ◽  
pp. 1379-1386 ◽  
Author(s):  
Maodong Zhang ◽  
Janet E. Hill ◽  
Champika Fernando ◽  
Trevor W. Alexander ◽  
Edouard Timsit ◽  
...  

2019 ◽  
Vol 20 (2) ◽  
pp. 163-181
Author(s):  
A. M. O'Connor ◽  
D. Hu ◽  
S. C. Totton ◽  
N. Scott ◽  
C. B. Winder ◽  
...  

AbstractWe conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sara Andrés-Lasheras ◽  
Reuben Ha ◽  
Rahat Zaheer ◽  
Catrione Lee ◽  
Calvin W. Booker ◽  
...  

A broad, cross-sectional study of beef cattle at entry into Canadian feedlots investigated the prevalence and epidemiology of antimicrobial resistance (AMR) in Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, bacterial members of the bovine respiratory disease (BRD) complex. Upon feedlot arrival and before antimicrobials were administered at the feedlot, deep nasopharyngeal swabs were collected from 2,824 feedlot cattle in southern and central Alberta, Canada. Data on the date of feedlot arrival, cattle type (beef, dairy), sex (heifer, bull, steer), weight (kg), age class (calf, yearling), source (ranch direct, auction barn, backgrounding operations), risk of developing BRD (high, low), and weather conditions at arrival (temperature, precipitation, and estimated wind speed) were obtained. Mannheimia haemolytica, P. multocida, and H. somni isolates with multidrug-resistant (MDR) profiles associated with the presence of integrative and conjugative elements were isolated more often from dairy-type than from beef-type cattle. Our results showed that beef-type cattle from backgrounding operations presented higher odds of AMR bacteria as compared to auction-derived calves. Oxytetracycline resistance was the most frequently observed resistance across all Pasteurellaceae species and cattle types. Mycoplasma bovis exhibited high macrolide minimum inhibitory concentrations in both cattle types. Whether these MDR isolates establish and persist within the feedlot environment, requires further evaluation.


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