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ARS Home Midwest Area Ames, Iowa National Animal Disease Center Virus and Prion Research Research





- Nicholson, Tracy
- Hau, Samantha
- 2023
- 2022
- Publications
- Animal Health (103)

Research Project: Virulence Mechanisms, Microbiome Changes and Control Strategies for Priority Bacterial Infections in Swine **Location:
                            Virus and Prion Research** 2023 Annual Report **Objectives**
                                

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. **Progress Report**
                                

Objective 1, Subobjective 1.1: The goal of this subobjective is to 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. Analysis of data arising from transcriptomic sequencing and proteomic analysis from G. parasuis samples collected from the infectious process have been conducted. This analysis will enable the identification of G. parasuis gene transcripts and proteins expressed during respiratory tract colonization and systemic disease that can be used in further virulence and vaccine studies. Whole-genome sequencing, assembly, and annotation for G. parasuis isolates obtained from swine production facilities within the U.S. have been completed. These genome assemblies have been screened for genes encoding any putative factors that could increase the capacity of these isolates to cause disease using both publicly available databases as well as published literature detailing experimentally verified virulence factors.

Objective 1, Subobjective 1.2: The goal of this subobjective is to 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. Phenotypic antimicrobial susceptibility testing has been performed and completed for G. parasuis isolates obtained from within the U.S.

Objective 2, Subobjective 2.1: The goal of this subobjective is to develop novel vaccines that can prevent clinical disease with priority bacterial pathogens of swine, such as G. parasuis and S. suis. Swine experiments have been completed to evaluate the efficacy of an individual protein from G. parasuis as a vaccine and its use as an additive to bacterin vaccines to enhance efficacy. Swine experiments have been completed to evaluate the application of an avirulent, bacteriocin producing strain of S. suis as a vaccine to prevent systemic disease with S. suis.

Objective 2, Subobjective 2.2: The goal of this subobjective is to identify immunogenic, protective, and conserved proteins of G. parasuis or S. suis through immunoproteomics that will be cross protective against multiple serotypes. Two-dimensional gel electrophoresis was completed, to probe immunogenic proteins of S. suis and Streptococcus equi subspecies zooepidemicus using serum from challenged animals. **Accomplishments**
                                

1. Streptococcus suis isolates obtained from within the U.S. did not harbor genes encoding the capacity to cause disease in humans. Most genomic sequence data needed to evaluate any potential risks attributed to S. suis is derived from isolates obtained outside the U.S. To help fill this gap, ARS researchers in Ames, Iowa, applied genome sequencing methods to examine the genetic makeup of S. suis isolates obtained within the U.S. These isolates were found to be genetically different from each other, indicating that they can give and receive genetic material from other bacteria. These isolates were also found to contain a high number of antimicrobial resistance genes, however, no genes encoding the capacity to cause disease in humans were found in these isolates. Collectively, this data provides a blueprint for addressing public and animal health concerns relating to the severity of disease caused by S. suis for producers, veterinarians, and public health officials. 2. Immunity to the key component of the outermost part of bacterial cell wall is not essential for protection against all Glaesserella parasuis strains. Glaesserella parasuis causes severe disease and death in pigs. It is a significant economic burden for pork producers. Producers control G. parasuis with vaccines, but research indicates vaccines may provide protection against only a single strain or capsule type (serotype). Capsule is a polysaccharide coating that surrounds bacteria and provides protection from the host immune system. To understand the role of capsule directed immunity in preventing G. parasuis disease, ARS researchers in Ames, Iowa, investigated the use of a G. parasuis mutant strain that does not produce a capsule as an inactivated vaccine. The capsule mutant vaccine was compared with a vaccine made from the wildtype strain (serotype 5). The capsule mutant protected pigs against the wildtype strain and multiple heterologous serotypes of G. parasuis including type 1, 4 and 13. However, when animals were challenged with a highly pathogenic serotype 5 strain, capsule specific protection was required for protection. These results are important to inform producers and veterinarians on the importance of strain selection for G. parasuis vaccines, especially for highly pathogenic isolates. This understanding will improve vaccine selection and reduce losses due to G. parasuis. 3. Bordetella bronchiseptica infection causes increases in the prevalence of other respiratory pathogens in swine. B. bronchiseptica causes respiratory infections in pigs, including pneumonia and atrophic rhinitis. It colonizes the nasal cavity and can alter the bacteria present (microbiota). To better understand the interactions between B. bronchiseptica and the normal microbiota of the nasal cavity, ARS researchers in Ames, Iowa, exposed pigs to B. bronchiseptica and compared the nasal microbiota between exposed and non-exposed pigs. This data shows the impact of B. bronchiseptica infection on the normal microbiota of the nasal cavity. Increases in respiratory pathogens following B. bronchiseptica exposure may contribute to the development of more complicated respiratory disease. This work contributes to the general understanding of the complex nature of respiratory infections in pigs and provides important information about interactions between B. bronchiseptica and other respiratory pathogens. This understanding will improve vaccine development and mitigation strategies for reducing economic losses due to B. bronchiseptica infection. 4. Bordetella bronchiseptica infection causes increased colonization but not disease with Streptococcus suis. B. bronchiseptica causes pneumonia in pigs and contributes to complex respiratory infections called porcine respiratory disease complex (PRDC). Coinfection with B. bronchiseptica increases the severity of disease with other respiratory pathogens. B. bronchiseptica infection can also increase nasal colonization with other pathogenic bacteria. S. suis is a systemic pathogen of pigs but also contributes to PRDC. To evaluate the interactions between B. bronchiseptica and S. suis, ARS researchers in Ames, Iowa, assessed colonization and disease in pigs exposed to B. bronchiseptica, S. suis, or both. Nasal colonization with S. suis was increased by coinfection with B. bronchiseptica; however, there was no increase in S. suis associated disease. Though no increase in disease was observed, increased colonization could have important implications when animals are stressed or immunocompromised, such as at weaning or during transport. This work provides important information on bacterial-bacterial interactions in the swine upper respiratory tract and contributes to the understanding of the role of B. bronchiseptica in PRDC as both a primary agent and contributor to more complicated infections is key information needed to develop vaccines needed to reduce losses due to B. bronchiseptica infection. **Review Publications**
                            *Hau, S.J., Devries, A.C., Brockmeier, S. 2022. Rapid application of long-acting ceftiofur can prevent death losses associated with Streptococcus equi subspecies zooepidemicus in pigs. Swine Health and Production. 30(5):292-297. https://doi.org/10.54846/jshap/1298.*
                                *Nicholson, T.L., Bayles, D.O. 2022. Comparative virulence and antimicrobial resistance distribution of streptococcus suis isolates obtained from the United States. Frontiers in Microbiology. 13. https://doi.org/10.3389/fmicb.2022.1043529.*
                                *Hau, S.J., Nielsen, D.W., Mou, K.T., Alt, D.P., Kellner, S., Brockmeier, S. 2023. Resilience of swine nasal microbiota to influenza A virus challenge in a longitudinal study. BMC Veterinary Research. 54:Article 38. https://doi.org/10.1186/s13567-023-01167-9.*
                                *Nicholson, T.L., Shore, S. 2022. Genome sequences of Streptococcus suis isolates obtained from pigs in the United States between 2015 and 2017. Microbiology Resource Announcements. 11(8):e01067-21. https://doi.org/10.1128/mra.01067-21.*


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