Current research focus

Funding: DFG, 482.000 EUR

Project Details:
Streptococcus suis is a frequent colonizer of the upper respiratory tract of pigs, but can also cause severe systemic diseases like meningitis and septicemia. However, pathogenesis of S. suis infection and the role of its virulence-associated factors, namely the pore-forming toxin suilysin (SLY) and the D-alanine-D-alanyl carrier ligase (DltA), is still not fully understood. So far, it is known that SLY damages different host cells by lytic pore formation and induces an inflammatory response leading to the release of cytokines, especially by monocytes/macrophages, and the recruitment of neutrophils. D-alanylation of lipoteichoic acids in the cell wall by DltA is known to increase resistance against antimicrobial peptides (AMPs) and phagocytosis of S. suis by neutrophils.
Our aim is to clarify the role of SLY and DltA in S. suis colonization of the porcine respiratory tract, systemic dissemination via the bloodstream, and invasion of the central nervous system. Thereby we will focus on their influence on innate immunity cells and the crosstalk between monocytes/macrophages and neutrophils. We hypothesize that the host compartments influence the expression of sly and dltA differentially and that vice versa SLY and DltA influence the host?s innate immune response by modulating the crosstalk between neutrophils and monocytes/macrophages contributing to the resistance of. S. suis towards immune defense mechanisms.
To investigate this, we will use complex in vitro cell culture systems that closely mimic the in vivo situation of the three main host compartments: a co-culture system of primary respiratory epithelial cells differentiated under air-liquid interface conditions and alveolar macrophages, porcine precision-cut lung slices, a reconstituted whole blood model, and the blood cerebrospinal fluid barrier model. Infection experiments will be performed with S. suis serotype 2 wild-type strain (wt), its isogenic mutants Δsly, ΔdltA, and ΔdltAΔsly as well as the respective complemented mutant strains.
We will start with the analysis of sly and dltA expression in the three compartments by quantitative real-time PCR and Western blotting, followed by the investigation of the neutrophil and the monocyte/macrophage response towards S. suis wt and sly- and dltA-deficient mutants. We will focus on the formation of neutrophil extracellular traps, reactive oxygen species production, phagocytic activity, and the release of certain cytokines and AMPs. Finally, we will investigate how secretions from monocytes/macrophages induced by S. suis infection influence neutrophils regarding their transmigration, inflammatory response, and phagocytic capacity, and vice versa.
The detailed investigation of the innate immune response towards S. suis infection in the three different compartments will help to better understand the switch of S. suis as a colonizer to an invasive pathogen, and how SLY and DltA are involved in this process.

Cooperation Partners:

Dr. Sophie Öhlmann (Institut für Bakteriologie und Mykologie, Veterinärmedizinische Fakultät, Universität Leipzig)

Funding: Bundesanstalt für Landwirtschaft und Ernährung (BLE), 554.060 EUR

Project Details:
Bacterial diarrhoeal diseases in pigs are of great economic importance, affect animal welfare in all age groups and contribute significantly to the use of antibiotics in pig. Of the seven Brachyspira species found in pigs, most diarrhoeal diseases are triggered by the species Brachyspira hyodsenteriae (BHY) and Brachyspira pilosicoli (BPI). Treatment of diarrhoea caused by brachyspiral infections is very time-consuming and only a small number of microbial agents are approved for treatment. The significance of differences in the pathogenic potential of different bacterial isolates and the influence of the genetic background of the pig is still unknown. Therefore, a reassessment of the brachyspirial infection to improve the animal welfare and reduce the use of antibiotics is needed. Consequently, the aim of the present project is to understand the pathogenesis of Brachyspira using our established in vitro intestinal organoid model. In addition, the influence of different Brachyspira species and the influence of different genetic backgrounds of the pigs will be investigated.

Project Details:
As part of the SeroFaSt - Mhyo project, a serological on-farm rapid test for the detection of
Mycoplasma hyopneumoniae infections in pigs. This test is intended to
differentiate between vaccinated and infected animals directly on the farm,
without the need for time-consuming and cost-intensive laboratory tests. The rapid identification of
infected animals should enable immediate, targeted treatment and thus lead to greater animal welfare and
and better consumer protection.

Project Details:
Frequencies of Glaesserella parasuis isolates resistant against various antimicrobial substances will be compared in the years 2006-2021

Results:

Wiencek I, Hartmann M, Merkel J, Trittmacher S, Kreienbrock L, Hennig-Pauka I. Temporal Patterns of Phenotypic Antimicrobial Resistance and Coinfecting Patho-gens in Glaesserella parasuis Strains Isolated from Diseased Swine in Germany from 2006 to 2021. Pathogens 2022; 11: 721. doi: 10.3389/fvets.2021.802570

Project Details:
The aim of this project is to characterize the situation of S. suis-related disease outbreaks on farms. The main influence of PRRSV circulation on farms, specific S. suis genotypes and pathotypes on tonsils and predefined environmental factors on the occurrence and development of S. suis-related disease will be assessed. The aim is to elaborate recommendations for practice with regard to outbreak prevention on farms.

Cooperation Partners:

Kooperationspartner des EU Projektes PigsSuis (PROGRAM FOR INNOVATIVE GLOBAL PREVENTION OF STREPTOCOCCUS SUIS, Referenznummer 727966

Project Details:
Frequencies of Actinobacillus pleuropneumoniae isolates resistant against various antimicrobial substances will be compared in the years 2006-2021. Frequencies of coinfecting agents will be determined.

Results:

doi: 10.3389/fvets.2021.802570