Development of Intranasal Bacterial Therapeutics to Mitigate the Bovine Respiratory Pathogen Mannheimia haemolytica
Date
2019-11
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Abstract
The emergence of multidrug-resistant pathogens associated with bovine respiratory disease (BRD) presents a significant challenge to the beef industry, as antibiotic administration is commonly used to prevent and control BRD in commercial feedlot cattle in North America. Thus, developing antibiotic alternatives such as bacterial therapeutics (BTs) to mitigate BRD is needed. Recent studies suggest that the nasopharyngeal (NP) microbiota, particularly lactic acid-producing bacteria (LAB), are important to bovine respiratory health and may be a source of BTs for the inhibition of BRD pathogens. The research presented in this thesis aimed to develop intranasal BTs to mitigate the BRD pathogen Mannheimia haemolytica and promote NP microbiota stability in feedlot cattle. Results from Study 1 showed that commercial probiotic bacteria were able to inhibit M. haemolytica growth and its adherence to epithelial cells. Study 2 revealed that the NP microbial community structure and relative abundance of LAB families underwent significant changes when cattle transported from the farm to an auction market, then to feedlot. Many of the LAB families were inversely correlated with the BRD-associated Pasteurellaceae family, and isolates from Lactobacillaceae, Streptococcaceae and Enterococcaceae families inhibited growth of M. haemolytica in vitro. This study provided evidence of potential antagonistic competition taking place between LAB and BRD-associated pathogens within the respiratory tract. Following these studies, using a targeted approach based on criteria evaluating M. haemolytica inhibition, adherence to turbinate cells, and immunomodulation, 6 Lactobacillus strains from an initial group of 178 bacterial isolates originating from nasopharynx of cattle were identified as the best BT candidates (Study 3). Intranasal inoculation of these BTs reduced colonization by M. haemolytica and induced modulation of respiratory microbiota in dairy calves experimentally challenged with M. haemolytica (Study 4). Finally, the longitudinal effects of intranasally administered BTs on the NP microbiota and the prevalence of BRD pathogens including Mannheimia were evaluated in post-weaned beef calves (Study 5). A single dose of intranasal BTs induced longitudinal modulation of the NP microbiota while showing no adverse effects on animal health and growth performance. With further characterization of inoculant dose and time of inoculation, the BTs may have potential for application as an antimicrobial alternative for mitigation of M. haemolytica in beef cattle.
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Keywords
Bacterial therapeutics, Bovine respiratory pathogen, Mannheimia haemolytica, Respiratory Microbiota, Lactobacillus
Citation
Amat, S. (2019). Development of Intranasal Bacterial Therapeutics to Mitigate the Bovine Respiratory Pathogen Mannheimia haemolytica (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.