Project Number: 6040-32000-009-013-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Apr 1, 2019
End Date: Mar 31, 2023
1. Determine changes in prevalence and genetic characteristics of MDR M. haemolytica over a 21-day receiving period in stocker cattle receiving or not receiving macrolide metaphylaxis, and/or subsequent AM therapy for clinical BRD. 2. Determine changes in the distribution of genomic sequences, known AMR genes (the resistome), and genetic elements associated with horizontal gene transfer in bacteria in stocker cattle receiving or not receiving macrolide metaphylaxis, and/or subsequent AM therapy. 3. Determine the effect of macrolide metaphylaxis on BRD morbidity and mortality in high-risk stocker cattle sampled for Objectives 1 and 2.
To complete Objectives 1, 2, and 3 we will purchase conventional high-risk stocker cattle and manage them using standard industry practice over a 21-day conditioning period. Cattle will be randomly assigned to two groups (n = 40 per group) to receive metaphylaxis (macrolide) or no antimicrobial. Three replicates will be done and the whole experiment will be repeated spring and fall of two years for a total of four experiments. Cattle that develop BRD over the 21-day study will be treated with a different AM class than the one they received for metaphylaxis. Cattle that develop BRD will be moved to a “hospital pasture” where they will stay for the duration of the study. Thus cattle that receive a second AM class for BRD treatment will not be in contact with cattle that receive only metaphylactic treatment on d. 0. This will allow us to identify mobile genetic elements (MGE) in cattle that have received only one AM for metaphylaxis (or no AM in the case of one group), which may be different than MGE isolated from cattle treated with a different AM class when they are sick. Cattle will be sampled by nasopharyngeal swab on study d. 0 and d. 21. All cattle treated for BRD will also be sampled before their first BRD treatment and on d. 21. M. haemolytica will be isolated from nasopharyngeal swabs. All M. haemolytica isolates will IDed by Vitec 2 and be tested for AM susceptibility by broth microdilution. Eleven isolates will be subjected to Whole Genome Sequencing, and MGE conferring resistance to 3 or more classes of AM will be identified in silico. Metagenomc analysis will also be done on all nasopharyngal swabs to determine the AR genes and mobile genetic elements present and their abundance. Metagenomics will also identify the populations of different bacteria, their abundance and changes after exposure to AM treatment. Together these methods will achieve objectives 1, 2, and 3.