Theses and Dissertations

ORCID

https://orcid.org/0000-0003-0140-3664

Advisor

Woolums, Amelia

Committee Member

Karisch, Brandi B.

Committee Member

Seo, Keun Seok

Committee Member

Morley, Paul S.

Committee Member

Frye, Jonathan G.

Date of Degree

5-10-2024

Original embargo terms

Visible MSU only 1 year

Document Type

Dissertation - Campus Access Only

Major

Veterinary Medical Science (Infectious Disease)

Degree Name

Doctor of Philosophy (Ph.D)

College

College of Veterinary Medicine

Department

Veterinary Medical Science Program

Abstract

Bovine respiratory disease (BRD) is the leading cause of morbidity in feeder and stocker cattle, resulting in large impacts on economics of stocker and feedlot operations. One of the most effective means of controlling BRD is the mass administration of antimicrobials (AM) at arrival or “metaphylaxis”, potentially leading to increased antimicrobial resistance (AMR). Mannheimia haemolytica (MH), the most commonly isolated bacterial pathogen in BRD cases in feedlot cattle, has been shown to have integrative-conjugative elements (ICE), which are mobile genetic elements that have the ability to integrate themselves in the host genome. Notably, these ICE have been shown to contain multiple antimicrobial resistance genes (ARG) conferring resistance to antimicrobial classes used for BRD treatment. ICE have also been shown to be transferred between different genera. Since these ICE contain genes for resistance to multiple AM classes, administration of one AM could increase pressure for bacteria to transfer ICE for resistance to multiple drug classes; therefore, mass administration of AM may lead to increased isolation of multidrug resistant (MDR) MH and increase presence of resistance genes in the metagenome. Many NGS studies to date have used low numbers of cattle or pooled samples due to cost. Pooling is an acceptable strategy to increase number of units sampled, however sequencing depth per individual sample is decreased, and there is little evidence comparing pools to individual samples. In a trial involving high risk stocker cattle, tulathromycin metaphylaxis was associated with increased isolation of MDR MH, and this was associated with ICE related genes. Using pooled DNA extracted from NPS in these animals, which were shown to be acceptable for group level comparisons, metaphylaxis also increased ARG richness and diversity in these heifers; however, BRD treatment and time had a greater effect on the mircrobiome and resistome. Further work is needed to improve MH strain classification. These finding highlight the complexity of AMR research, because though tulathromycin had a clear effect on odds of isolation of MDR MH, metaphylaxis’ effects on the resistome and microbiome were more complex, and time and BRD contributed to greater change.

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