scholarly journals Development of Bacterial Therapeutics against the Bovine Respiratory Pathogen Mannheimia haemolytica

2019 ◽  
Vol 85 (21) ◽  
Author(s):  
Samat Amat ◽  
Edouard Timsit ◽  
Danica Baines ◽  
Jay Yanke ◽  
Trevor W. Alexander
Keyword(s):  
Respiratory Disease ◽  
Animal Health ◽  
Bovine Respiratory Disease ◽  
Feedlot Cattle ◽  
Mitigation Strategies ◽  
Commensal Bacteria ◽  
Mannheimia Haemolytica ◽  
Respiratory Pathogen ◽  
Content Type

ABSTRACT Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in beef cattle. Recent evidence suggests that commensal bacteria of the bovine nasopharynx have an important role in maintaining respiratory health by providing colonization resistance against pathogens. The objective of this study was to screen and select bacterial therapeutic candidates from the nasopharynxes of feedlot cattle to mitigate the BRD pathogen Mannheimia haemolytica. In a stepwise approach, bacteria (n = 300) isolated from the nasopharynxes of 100 healthy feedlot cattle were identified and initially screened (n = 178 isolates from 12 different genera) for growth inhibition of M. haemolytica. Subsequently, selected isolates were evaluated for the ability to adhere to bovine turbinate (BT) cells (n = 47), compete against M. haemolytica for BT cell adherence (n = 15), and modulate gene expression in BT cells (n = 10). Lactobacillus strains had the strongest inhibition of M. haemolytica, with 88% of the isolates (n =33) having inhibition zones ranging from 17 to 23 mm. Adherence to BT cells ranged from 3.4 to 8.0 log10 CFU per 105 BT cells. All the isolates tested in competition assays reduced M. haemolytica adherence to BT cells (32% to 78%). Among 84 bovine genes evaluated, selected isolates upregulated expression of interleukin 8 (IL-8) and IL-6 (P < 0.05). After ranking isolates for greatest inhibition, adhesion, competition, and immunomodulation properties, 6 Lactobacillus strains from 4 different species were selected as the best candidates for further development as intranasal bacterial therapeutics to mitigate M. haemolytica infection in feedlot cattle. IMPORTANCE Bovine respiratory disease (BRD) is a significant animal health issue impacting the beef industry. Current BRD prevention strategies rely mainly on metaphylactic use of antimicrobials when cattle enter feedlots. However, a recent increase in BRD-associated bacterial pathogens that are resistant to metaphylactic antimicrobials highlights a pressing need for the development of novel mitigation strategies. Based upon previous research showing the importance of respiratory commensal bacteria in protecting against bronchopneumonia, this study aimed to develop bacterial therapeutics that could be used to mitigate the BRD pathogen Mannheimia haemolytica. Bacteria isolated from the respiratory tracts of healthy cattle were characterized for their inhibitory, adhesive, and immunomodulatory properties. In total, 6 strains were identified as having the best properties for use as intranasal therapeutics to inhibit M. haemolytica. If successful in vivo, these strains offer an alternative to metaphylactic antimicrobial use in feedlot cattle for mitigating BRD.

scholarly journals Closed Genome Sequences and Antibiograms of 16 Pasteurella multocida Isolates from Bovine Respiratory Disease Complex Cases and Apparently Healthy Controls

2018 ◽  
Vol 7 (11) ◽  
Author(s):  
Gregory P. Harhay ◽  
Dayna M. Harhay ◽  
James L. Bono ◽  
Timothy P. L. Smith ◽  
Sarah F. Capik ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Pasteurella Multocida ◽  
Bacterial Species ◽  
Bovine Respiratory Disease ◽  
Opportunistic Pathogen ◽  
Feedlot Cattle ◽  
Content Type ◽  
Disease Complex ◽  
Bovine Respiratory Disease Complex ◽  
Apparently Healthy

Pasteurella multocida is an animal-associated Gram-negative member of the Pasteurellaceae family. It is an opportunistic pathogen and is one of the principal bacterial species contributing to bovine respiratory disease complex (BRDC) in feedlot cattle.

Factors associated with Bovine Respiratory Disease case fatality in feedlot cattle

2021 ◽  
Author(s):  
C Blakebrough-Hall ◽  
P Hick ◽  
T J Mahony ◽  
L A González
Keyword(s):  
Respiratory Disease ◽  
Nasal Swab ◽  
Animal Health ◽  
Bovine Respiratory Disease ◽  
Case Fatality ◽  
Mixed Effects ◽  
Feedlot Cattle ◽  
Blood Metabolites ◽  
Factors Associated ◽  
Production Factors

Abstract Bovine Respiratory Disease (BRD) is the primary cause of morbidity and mortality in cattle feedlots. There is a need to understand what animal health and production factors are associated with increased mortality risk due to BRD. The aim of the present study was to explore factors associated with BRD case fatality in feedlot cattle. Four pens totalling 898 steers were monitored daily for visual signs of BRD such as difficult breathing and coughing, and animals exhibiting signs of BRD were taken to the hospital shed for further examination and clinical measures. Blood samples were obtained at feedlot entry and at time of first BRD pull from animals diagnosed with BRD (n=121) and those that died due to BRD confirmed by post-mortem examination (n=16; 13.2% case fatality rate). Mixed-effects linear regression models were used to estimate differences in animal health and production factors and the relative concentrations of 34 identified blood metabolites between animals that survived versus those that died. Generalised linear mixed-effects models were used to obtain the odds of being seronegative (at both feedlot entry and first BRD pull) to five BRD viruses and having a positive nasal swab result at the time of first pull in died and survived animals. Animals that died from BRD had lower average daily gain (ADG), reduced weight at first BRD pull, higher visual BRD scores and received more treatments for BRD compared to animals that survived BRD (P &lt; 0.05). The odds of being seronegative for bovine viral diarrhea virus 1 (BVDV-1) was 5.66 times higher for animals that died compared to those that survived (P = 0.013). The odds of having a positive bovine coronavirus nasal swab result were 13.73 times higher in animals that died versus those that survived (P = 0.007). Animals that died from BRD had higher blood concentrations of α glucose chain, β-hydroxybutyrate, leucine, phenylalanine and pyruvate compared to those that survived (P &lt; 0.05). Animals that died from BRD had lower concentrations of acetate, citrate and glycine compared to animals that survived (P &lt; 0.05). The results of the current study suggest that ADG to first BRD pull, weight at first BRD pull, visual BRD score, the number of BRD treatments, seronegativity to BVDV-1, virus positive to BCoV nasal swab, and that certain blood metabolites are associated with BRD case fatality risk. The ability of these measures to predict the risk of death due to BRD needs further research.

scholarly journals Intranasal Bacterial Therapeutics Reduce Colonization by the Respiratory Pathogen Mannheimia haemolytica in Dairy Calves

mSystems ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Samat Amat ◽  
Trevor W. Alexander ◽  
Devin B. Holman ◽  
Timothy Schwinghamer ◽  
Edouard Timsit
Keyword(s):  
Total Mortality ◽  
Mannheimia Haemolytica ◽  
Dairy Calves ◽  
Respiratory Pathogen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Rrna Gene ◽  
Nasal Colonization ◽  
Content Type ◽  
Nasal Microbiota

ABSTRACT Six Lactobacillus strains originating from the nasopharyngeal microbiota of cattle were previously characterized in vitro and identified as candidate bacterial therapeutics (BTs) for mitigating the bovine respiratory pathogen Mannheimia haemolytica. In the present study, these BT strains were evaluated for their potential to (i) reduce nasal colonization by M. haemolytica, (ii) modulate the nasal microbiota, and (iii) stimulate an immune response in calves experimentally challenged with M. haemolytica. Twenty-four Holstein bull calves (1 to 3 weeks old) received either an intranasal BT cocktail containing 6 Lactobacillus strains (3 × 109 CFU per strain; BT + Mh group) 24 h prior to intranasal M. haemolytica challenge (3 × 108 CFU) or no BTs prior to challenge (Mh, control group). Nasal swab, blood, and transtracheal aspiration samples were collected over the course of 16 days after BT inoculation. Counts of M. haemolytica were determined by culturing, and the nasal and tracheal microbiotas were evaluated using 16S rRNA gene sequencing. Serum cytokines (interleukin-6 [IL-6], IL-8, and IL-10) were quantified by enzyme-linked immunosorbent assay (ELISA). Administration of BT reduced nasal colonization by M. haemolytica (P = 0.02), modified the composition and diversity of the nasal microbiota, and altered interbacterial relationships among the 10 most relatively abundant genera. The BT + Mh calves also had a lower relative abundance of Mannheimia in the trachea (P < 0.01) but similar cytokine levels as Mh calves. This study demonstrated that intranasal BTs developed from the bovine nasopharyngeal Lactobacillus spp. were effective in reducing nasal colonization by M. haemolytica in dairy calves. IMPORTANCE Bovine respiratory disease (BRD) is one of the significant challenges for the modern dairy industry in North America, accounting for 23 to 47% of the total mortality among pre- and postweaned dairy heifers. Mass medication with antibiotics is a common practice to control BRD in dairy cattle. However, the emergence of multidrug-resistant BRD pathogens highlights the importance of developing alternatives to antibiotics for BRD mitigation. Using a targeted approach, we recently identified 6 Lactobacillus strains originating from the bovine respiratory microbiota as candidates to be used as bacterial therapeutics (BTs) for the mitigation of the BRD pathogen Mannheimia haemolytica. Here, we demonstrated that intranasal inoculation of the BT strains reduced nasal colonization by M. haemolytica in dairy calves experimentally challenged with this pathogen. This study, for the first time, shows the potential use of intranasal BTs as an alternative to mitigate BRD pathogens in cattle.

scholarly journals A systematic review and network meta-analysis of injectable antibiotic options for the control of bovine respiratory disease in the first 45 days post arrival at the feedlot

2019 ◽  
Vol 20 (2) ◽  
pp. 163-181
Author(s):  
A. M. O'Connor ◽  
D. Hu ◽  
S. C. Totton ◽  
N. Scott ◽  
C. B. Winder ◽  
...  
Keyword(s):  
Systematic Review ◽  
Beef Cattle ◽  
Respiratory Disease ◽  
Citation Index ◽  
Meta Analysis ◽  
Bovine Respiratory Disease ◽  
The United States ◽  
Feedlot Cattle ◽  
Freedom Of Information ◽  
Biological Index

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.

Serotyping and antimicrobial resistance of Mannheimia haemolytica strains from European cattle with bovine respiratory disease

2019 ◽  
Vol 124 ◽  
pp. 10-12 ◽  
Author(s):  
Sara Andrés-Lasheras ◽  
Rahat Zaheer ◽  
Cassidy Klima ◽  
Haley Sanderson ◽  
Rodrigo Ortega Polo ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Respiratory Disease ◽  
Bovine Respiratory Disease ◽  
Mannheimia Haemolytica ◽  
European Cattle
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