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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PIGSs (Program for Innovative Global Prevention of Streptococcus suis.)

Teaser

Summary

The problems addressed by PIGSs (Program for Innovative Global prevention of Streptococcus suis) are the major economic losses to the pig production industry worldwide and the animal health burden caused by infections with the bacterium Streptococcus suis. This pathogen can cause invasive disease in pigs with symptoms such as acute sepsis, meningitis, endocarditis, pneumonia and arthritis often being reported. Almost 100% of pig farms worldwide have carrier animals. Whether or not S. suis causes disease in pigs depends on pathogen factors, hosts factors, environmental factors and their interactions. It depends on the genetic constitution of the microbial pathogen as well as on the susceptibility of the host which can be influenced by co-infection, age, immunity, microbiota etc. In addition, environmental factors such as stress and hygiene factors may influence the interaction by altering host or microbiota or â€˜behaviourâ€™ (referring to a neutral commensal carriage - or virulent state) of the pathogen. This knowledge will be used to develop innovations for disease prevention through vaccination, promoting colonization resistance to S. suis and stimulating innate immunity in young piglets. Additionally, the knowledge generated will lead to the development of diagnostic markers for disease-causing strains which will for the first time make it possible to study infection dynamics on farms and identify risk factors in farming practices as well as strategies to prevent or control disease outbreaks. A major goal of the PIGSs project is to increase our understanding of the host-pathogen-environment interactions in S. suis infections in pigs, and thereby strengthening the evidence base for new innovations and effective prevention and control strategies.

Work performed

The first months of the project were dedicated to implement the management bodies, put in place all recruitment activities and to ensure a smooth workflow between all partners from the beginning. From the scientific perspective WP1 is at the heart of the project and is concerned with building a global collection of S. suis isolates. WP1 delivers a better knowledge of the genomic diversity and the roles of genes involved in virulence and environmental survival of S. suis. We have now obtained a large S. suis strain in major pig producing countries across Europe through cooperation and contracts with veterinary diagnostic laboratories in each country. This strain collection was complemented by isolates sent to us from USA, North America and China. The genomic analysis of the entire collection will be complete around April 2019.
WP2 will determine which S. suis genes are expressed at different anatomical sites in vivo and which genes are essential for survival and growth in the ecological niches within the host. The main results so far include Tnseq data from S. suis to identify genes required for growth and virulence of S. suis during infection â€œconditional essential genesâ€. We also started experiments using air-liquid interface (ALI) cell cultures and precision-cut lung slice cultures with selected mutants showing a phenotype in biofilm assays. We also established porcine and human intestinal organoids for studying adherence and invasion of wild-type and genetic mutants of S. suis strains.
WP3 focuses on the characterization of the microbiome and characterization of the innate immune response to infection/colonization by S. suis. We have investigated the innate response to S. suis infection and colonization in vivo using a virulent (S10) and a non-virulent (T15) strains of S. suis. Preliminary data on the innate immune response indicates differences between the control non-infected group and the 2 infected groups, and more interestingly, differences between the two infected groups.
WP4 will elucidate how co-infections are studied of either swine influenza (SIV) or Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and S. suis contributes to disease and explain failure of interventions. Using the ALI model, it was shown that the co-infection of either H3N2 or H1N1 SIV virus with S. suis strain 10 did not induce synergistic effects on cytotoxicity. Co-infection of SIV and S. suis on porcine PCLS showed that replication of SIV is decreased after prior infection with S. suis. To study the interaction between PRRSV and S. suis, a co-culture system was set-up. S. suis infected PCSL were co-cultured with Porcine Alveolar Macrophages (PAMs) infected with PRRSV. Different serotypes of S. suis as well as different genotypes of PRRSV were included in the experiments.
WP5 will quantify the burden of disease caused by S. suis, determine the main risk factors associated with clinical cases of S. suis and perform a targeted systematic surveillance of zoonotic S. suis infections in participating European countries with intensive pig production. Till now, data is still being gathered it has not been possible to obtain homogeneous information from different countries. We also discussed and planned the different aspects related to the case control study. Furthermore, we defined the types of farms to include in the study and the characteristics that have to fulfill the cases and the controls.
WP6 is concerned with developing broadly cross-protective vaccines for young pigs based on protein antigens which are immunogenic, expressed in vivo in the blood and tissues and are surface accessible to antibodies to favor opsonization of S. suis. The main results so far have been the identification of conserved genes in 1,079 genomes diseased-associated isolates across different geographical regions. We used a pipeline of software tools for the prediction of vaccine candidates and compiled a list of conserved surface or secreted proteins co

Final results

Control of S. suis in pig herds is in general hampered by the lack of vaccines that provide protection against multiple serotypes and strains. This is due to the high genotypic, phenotypic and geographic variability that exits among strains, between and within serotypes. One of our ambitions is to develop a global cross-protective protein subunit vaccine through the use of GWAS to select antigen candidates that are conserved in disease-causing isolates. This innovative and novel approach of combining GWAS and reverse vaccinology will only become possible because of our ambition to sequence a large global collection of isolates from all major pork-producing regions of the world. The second ambition is to develop innovations in diagnostics for disease-causing strains of S. suis based on GWAS. This original idea will overcome the inability to distinguish virulent disease-causing strains from non-virulent strains. Addressing this issue will for the first time, allow use of diagnostics to guide antibiotic metaphylaxis and vaccination use to control S. suis outbreaks. This increases efficiency and contributes to the reduction of antibiotic use in pig farming.

Longer-term the PIGSs project expects to contribute to substantially reducing S. suis disease in pigs and thereby in animal health and welfare.