Epidemiological investigation of antimicrobial resistance in beef production using metagenomic sequencing
Date
2019
Authors
Doster, Enrique, author
Hoover, Edward A., advisor
Morley, Paul S., advisor
Belk, Keith E., committee member
Abdo, Zaid, committee member
Gow, Sheryl P., committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Globally, the emergence of antimicrobial resistance (AMR) resulting in treatment failure is recognized as a growing public health threat. Antimicrobial use practices used in beef production are thought to be a direct driver of increasing antimicrobial resistance in pathogens and the environment, in part due to the higher volumes of antimicrobial drug necessary to treat cattle weighing 10 times more than an average person. This has led policy makers and public health organizations to promote "judicious use" or outright ban of antimicrobial drugs in livestock production. Use of antimicrobials is unavoidable for the treatment of disease and we must therefore learn how we can best adjust our AMD use to reduce selection of AMR pathogens. However, outside of important indicator organisms and pathogens, little is known about how different antimicrobial drug use practices affect communities of microorganisms, or microbiomes, and the AMR gene determinants, or resistome, shared between pathogen and non-pathogens alike. With advances in high-throughput sequencing (HTS), we can perform culture-independent studies and gain a better understanding of how antimicrobial drug use practices in livestock production affect AMR epidemiology. This dissertation consists of five studies that employ HTS to characterize the microbiome and resistome of samples with differing AMD exposure along the beef production line. Projects begin with a look into the short-term effects on the microbiome and resistome of feedlot cattle following treatment with a macrolide drug, tulathromycin, in the manuscript "Investigating Effects of Tulathromycin Metaphylaxis on the Fecal Resistome and Microbiome of Commercial Feedlot Cattle Early in the Feeding Period". Fecal samples collected in this project also were processed with aerobic culture, polymerase chain reaction (PCR), and lateral flow immunoassay for identification of Salmonella enterica and the comparison of these results are presented in "A Cautionary Report for Pathogen Identification Using Shotgun Metagenomics; a Comparison to Aerobic Culture and Polymerase Chain Reaction for Salmonella enterica Identification". Samples collected as part of a longitudinal study in feedlot cattle were analyzed to characterize the associations between AMD use and AMR in two bacterial species. These archived samples are leveraged for a broader understanding of AMR dynamics by adding a community-level perspective to results from aerobic culture. Results in individual cattle are presented in "Antimicrobial Drug Use in Beef Feedlots; Effects on the Microbiome and Resistome Dynamics in Individual Cattle" and results at the pen-level in "Metagenomic Investigation of the Effects of Antimicrobial Drug Use Practices on the Microbiome and Resistome of Beef Feedlot Cattle". Finally, in "Metagenomic Characterization of the Microbiome and Resistome in Retail Ground Beef" we examined the end of the beef production line by comparing the microbiome and resistome of retail ground beef products from either conventional production systems or those labeled as "raised with antibiotics" (RWA). The five studies presented in this dissertation each contribute to the collective understanding of how AMD use in livestock production system can affect the ecology of AMR in microbial communities. These projects are useful first steps in learning to manage AMR in beef production systems; encompassing a targeted look at the use of one type of AMD, characterizing the resistome dynamics in individual cattle and pens over time in a feedlot, a comparison of the resistome in ground beef products, and many other aspects of AMR epidemiology. The final study, describing limits to incorporating HTS for pathogen identification, serves as a cautionary reminder that with new technologies come new challenges and that research must keep pace.
Description
Rights Access
Subject
beef production
metagenomic sequencing
resistome
epidemiology
antimicrobial resistance
microbiome