Development of bacterial therapeutics against the bovine respiratory pathogen Mannheimia haemolytica

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.