Theses and Dissertations

ORCID

https://orcid.org/0009-0006-3645-7864

Issuing Body

Mississippi State University

Advisor

Woolums, Amelia R.

Committee Member

Seo, Keun S.

Committee Member

Lawrence, Mark

Committee Member

Meyer, Florencia

Committee Member

Wills, Robert

Date of Degree

12-13-2024

Original embargo terms

Visible MSU only 2 years

Document Type

Dissertation - Campus Access Only

Major

Veterinary & Biomedical Sciences (Infectious Disease)

Degree Name

Doctor of Philosophy (Ph.D.)

College

College of Veterinary Medicine

Department

Department of Pathobiology and Population Medicine

Abstract

Bovine respiratory disease (BRD) is a major economic concern in the North American beef cattle industry. BRD results from the interaction of environmental factors, inadequate host immunity, and viral and bacterial pathogens. With bacteria being the leading pathogen and Mannheimia haemolytica being the most frequent bacteria isolated from diseased cattle, antimicrobial metaphylaxis has been used as the main mitigation strategy. Metaphylaxis has been shown to be effective in managing bacterial BRD but has contributed to the emergence of antimicrobial-resistant microbes, posing risks to animal and public health. Antimicrobial peptides (AMPs) have emerged as promising alternatives to antimicrobials due to their broad-spectrum activity against various pathogens. This research investigates the potential of bovine myeloid antimicrobial peptide-28 (BMAP-28), its modified synthetic version Syn-1, and bactenecin-5 (Bac-5) as novel treatments for BRD pathogens. We assessed their in vitro efficacy against BRD pathogens, including Mannheimia haemolytica, bovine respiratory syncytial virus (BRSV), and bovine herpesvirus 1 (BHV-1). BMAP-28 and Syn-1 showed significant antimicrobial activity, inhibiting bacterial growth and viral replication. Notably, combined application of BMAP-28 and Bac-5 showed enhanced efficacy, with reduced minimum inhibitory concentrations (MICs) compared to individual peptides. In this research, the use of mRNA as a delivery tool for antimicrobial peptides to overcome challenges associated with peptide stability and delivery in cell culture was also investigated. Although initial tests revealed no significant antimicrobial effect from mRNA-transfected cells, the use of mRNA to activate endogenous cathelicidin genes showed promise. This study highlights the potential of AMPs and mRNA-based delivery systems as alternatives to antimicrobials for managing BRD. Future research should focus on optimizing mRNA technology for peptide expression and evaluating these methods in live animals to establish effective prevention and treatment strategies for BRD and other diseases in cattle.

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