Location: Virus and Prion Research
Project Number: 5030-32000-237-000-D
Project Type: In-House Appropriated
Start Date: Oct 6, 2021
End Date: Oct 5, 2026
Objective:
Objective 1: Investigate the role of virulence mechanisms and impact on the swine respiratory microbiota of priority, emerging or re-emerging pathogens such as Glaesserella parasuis and Streptococcus suis. This includes evaluating the presence and mechanisms of transfer of antimicrobial resistance (AMR) genes harbored by these bacterial pathogens.
Subobjective 1.1: Identify genetic determinants contributing to the virulence of G. parasuis and S. suis through the use of comparative genomics, functional genomics, and proteomics.
Subobjective 1.2: Evaluate the presence of AMR genes, determine the genomic location of identified AMR genes, and determine which specific type of MGEs most abundantly contain AMR genes harbored by priority, emerging or re-emerging swine bacterial pathogens.
Subobjective 1.3: Determine the impact of infection with priority swine pathogens on the respiratory microbiota and development of secondary bacterial infections.
Objective 2: Develop and evaluate novel non-antibiotic intervention and management strategies to control priority bacterial diseases in swine, including vaccine platforms and therapeutics.
Subobjective 2.1: Develop novel vaccines and therapeutics to prevent clinical disease or decrease colonization caused by priority, emerging or re-emerging swine bacterial pathogens.
Subobjective 2.2: Evaluate the host response to vaccination or infection with bacterial pathogens such as G. parasuis or S. suis to identify mechanisms of cross protective immunity.
Approach:
The first goal for this research plan is to investigate the role of virulence mechanisms and impact on the swine respiratory microbiota of priority, emerging or re-emerging pathogens such as Glaesserella parasuis and Streptococcus suis. This includes evaluating the presence and mechanisms of transfer of antimicrobial resistance (AMR) genes harbored by these bacterial pathogens. First, we will use genome sequence data to identify genes encoding virulence factors and compare population structure of isolates, determine whether and how bacterial gene and protein expression responds to mammalian host signals, and determine which genes enable bacteria to colonize the swine respiratory tract and cause invasive disease. Next, we will compare the whole genome sequences of swine bacterial pathogens to identify AMR genes and determine whether or not identified AMR genes are located within mobile genetic elements (MGEs) such as plasmids, prophages, integrative and conjugative elements (ICEs), insertion sequences, and transposons. Finally, we will determine whether and how the microbiota changes following infection with swine respiratory pathogens and whether changes contribute to enhanced disease and evaluate the impact of pathogen-pathogen interactions occurring during infections with G. parasuis or S. suis. The second goal for this research plan is to develop and evaluate novel non-antibiotic intervention and management strategies to control priority bacterial diseases in swine, including vaccine platforms and therapeutics. First, we will develop novel vaccines that can prevent clinical disease with priority bacterial pathogens of swine, such as G. parasuis and S. suis. Examples of these novel vaccines include a G. parasuis capsule mutant bacterin, protein subunit vaccines for S. suis and G. parasuis, a S. suis capsule mutant, a conjugated capsule vaccine for G. parasuis, and a SEZ bacterin vaccine. We will additionally isolate bacteriophages active against swine LA-MRSA ST398 isolates and evaluate the use of bacteriophage treatment to reduce colonization. Finally, we will identify immunogenic, protective, and conserved outer membrane proteins of G. parasuis through immunoproteomics that will be cross protective against multiple serotypes.
