The head of our bacteriological research group, Prof. Christoph G. Baums, and his colleagues are investigating infections caused by streptococci, brachyspires and Klebsiellae in various projects. The Bacteriology group also focuses on vaccine research, the development of innovative diagnostic methods and alternative treatment options for infections. The research projects are embedded in the focal points of the Centre for Infectious Diseases.

One focus of the Bacteriology group is the investigation of S. suis, the most important bacterial pathogen in modern pig husbandry. Foto: Christoph Baums

Projects of the Streptococcus suis group

Streptococcus (S.) suis is one of the most important bacterial pathogens in modern pig farming. Infections with S.suis pathogens cause great economic losses worldwide and are the main indication for the use of antibiotics in pigs. Meningitits, septicaemia, endocarditis and arthritis are import manifestations of  S. suis infections. Furthermore, in humans this pathogen is responsible for serious illnesses like meningitis. Due to its zoonotic potential, the lack of an approved vaccine and the severity of disease, there is a huge need for research in the field of basic research and vaccine development.

Project

Development of vaccines against respiratory and systemic infections in pigs (Project 3 of the collaborative research project VacoME)

Objectives

A main objective of the collaborative research project VacoME funded by Infect Control 2020 (http://www.infectcontrol.de/de/vacome.html) is the identification of host compartment-specific antigens of Streptococcus suis, which alone or in combination elict protection against infections caused by these pathogens.

Summary

The zoonotic pathogen S. suis is the most important invasive bacterial pathogen in piglet raising facilities. It causes septicemia and meningitis. Both are associated with high losses. The collaboration VacoME of the research association Infect Control 2020 targets the identification and validation of protective antigens of S. suis, which exhibit increased expression in in vivo proteomics- und RNAseq-analysis in different host compartments and are recognized by reconvalescence sera. For this, bacteria are isolated from the different host compartments after infection of piglets with S. suis. Important host compartments for this pathogen are the respiratory mucosa, blood and cerebrospinal fluid. Proteom and transcriptom analysis are conducted right after isolation. After recombinant expression of the identified factors immunoproteomic analysis will be conducted using porcine reconvalescence sera. The humoral and cellular immune responses will be characterised for selected streptococcal antigens to identify ex vivo correlates for protective immunity. This will be used to establish an ex vivo approach, which allows to predict also the protective efficacy of vaccine candidates for other pathogens. The goal of this transsectoral approach is to demonstrate, that a selective combination of immunogens allows to generate a vaccine elicting protection against different serotypes of S. suis infections.

Project Manager

Prof. Christoph G. Baums

Participating Associates

Publications

Ebner F, Schwiertz P, Steinfelder S, Pieper R, Zentek J, Schütze N, Baums CG, Alber G, Geldhof P, Hartmann S. 2017. Pathogen-Reactive T Helper Cell Analysis in the Pig. Front Immunol. 8:565. doi: 10.3389/fimmu.2017.00565

Cooperation Partners

  • Prof. Sven Hammerschmidt, Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt University Greifswald
  • Prof. Uwe Völker, Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt University Greifswald
  • Prof. Gottfried Alber, Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig
  • Prof. Susanne Häußler, Research Group Molecular Bacteriology, Helmholtz Centre for Infection Research
  • Dr. Peter Schmid, Area Animal Health, IDT Biologika
  • Dominik Driesch, BioControl Jena GmbH

Founding

Federal Ministry of Education and Research

Project

Investigations on the development of a vaccine that provides serotype-spanning protection against S. suis infections after early application.

Objectives

In this project, the immune response to a S. suis vaccine will be investigated.

Summary

The prophylaxis of S. suis infections is very difficult because no vaccine is approved in Europe. In many cases, whole groups of pigs are treated with antibiotics in order to control the stock problems with this pathogen. Together with our industrial partner, IDT Biologika GmbH, we are investigating the protective and immunogenic effect of selected bacterial antigens in order to advance the development of vaccines against this pathogen. The immune response of pigs to the vaccine and the infection will be investigated in more detail. The project is carried out in close cooperation with the Institute of Immunology of the Faculty of Veterinary Medicine, which in particular records the antigen-specific leukocytes of the experimental pigs.

Project Manager

Prof. Christoph G. Baums

Participating Associates

Publications

Rieckmann K, Müller K, Moter A, Baums CG, Seydel A. 2017. Streptococcus suis serotype 9 endocarditis and subsequent severe meningitis in a growing pig despite specific bactericidal humoral immunity. JMM Case Rep. ;4:e005093. doi: 10.1099/jmmcr.0.005093

Cooperation Partners

  • Prof. Gottfried Alber and Dr. Nicole Schütze, Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig

Founding

IDT Biologika GmbH

Project

Formation of neutrophilic extracellular networks in the S. suis-infected cerebrospinal fluid compartment

Objectives

Role of extracellular networks (NETs) formed by neutrophilic granulocytes in S. suis-Meningitis

Summary

The course of S.suis infections is highly complex and is still relatively poorly understood. A typical sign of S.suis infection is the infiltration of infected tissues with numerous neutrophilic granulocytes. Neutrophilic granulocytes form extracellular networks (NETs), which were recently identified as an important immune defense mechanisms against different pathogens. Their functions in S.suis infections and in meningitis has not yet been studied. Preliminary studies indicate, that S. suis is capable of triggering human and porcine NETs formation. However, S. suis can also successfully escape capturing by nets by degrading them with DNases. In this project we test the hypothesis, that NETs formation and S.suis NETs degradation influence the disease course of S.suis meningitis. Therefore, we use a human and porcine model of the blood-cerebrospinal fluid barrier. For in vivo experiments we use the pig as natural host. Aim of the study is to elucidate the role of NETs in the pathogenesis of S.suis meningitis.

Project Manager

  • Prof. Christoph G. Baums
  • Prof. Maren Köckritz-Blickwede, Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Foundation

Participating Associates

Sophie Öhlmann

Cooperation Partners

  • Prof. Horst Schroten and Prof. Tobias Tenenbaum, Clinic for Pediatrics and Youth Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University Heidelberg
  • Prof. Andreas Beineke, Institute of Pathology, University of Veterinary Medicine Hannover, Foundation (TiHo)
  • Prof. Gottfried Alber and PD Uwe Müller, Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig

Founding

Deutsche Forschungsgemeinschaft

 

Project

Immunoglobulin M-degrading enzyme of Streptococcus suis (IdeSsuis): modulation of B-cell function and consequences for mucosal colonization

Objectives

Elucidation of IdeSsuis-dependent modulation of the adaptive immune response during mucosal colonization

Summary

Streptococcus suis (S. suis) is one of the most important porcine pathogens and an emerging human pathogen. In pigs, S. suis colonizes very efficiently the upper respiratory mucosa including nasopharynx, tonsils (the putative entry port) and the retropharyngeal lymph nodes. S. suis is unique among bacterial pathogens in expressing immunoglobulin (Ig) M degrading enzyme, designated IdeSsuis. Cleavage of IgM by IdeSsuis might be relevant for S. suis colonisation of mucosal surfaces where IgM concentrations are lower than in serum. Thus, we hypothesise that IdeSsuis-mediated IgM proteolysis by colonising streptococci is sufficient to diminish IgM-dependent effector functions in compartment. Colonisation of S. suis-free piglets with wild type and mutant S. suis strains will be induced experimentally to quantitatively determine colonisation efficacy and IgM degradation on mucosal surfaces. We will test the hypothesis that S. suis-expressed IdeSsuis is effective on B cells expressing membrane IgM (i.e. B cell receptor, BCR) especially at mucosal sites of colonisation. Recently, we have shown that IdeSsuis cleaves both soluble IgM and IgM-BCR on B cells, which is thought to reduce mucosal B cell response and antibody formation against S. suis.

Experimental colonisation of the upper respiratory tract of S. suis-free piglets with encapsulated S. suis or its unencapsulated isogenic mutant will be conducted to analyse B-like cells activated by capsular polysaccharides. In a further animal experiment we specifically investigate the hypothesis that S. suis colonisation modulates adaptive immunity through IgM cleavage by IdeSsuis at mucosal sites leading to impaired protective immunity upon challenge. This experiment will include comparison of state-of-the-art complemented S. suis mutants expressing either wild type IdeSsuis or a point-mutated variant of IdeSsuis deficient in IgM cleavage. The project is expected to lead to a better understanding of the role of IgM degradation during colonisation and to explain why IgM proteolysis is a highly conserved phenotype in all investigated S. suis serotypes.

Project Manager

  • Prof. Christoph G. Baums
  • Prof. Gottfried Alber, Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig

Cooperation Partners

  • Prof. Andreas Beineke, Institute of Pathology, University of Veterinary Medicine Hannover, Foundation (TiHo)
  • Prof. Ralf Hoffmann, Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), University Leipzig
  • Prof. Peter Valentin-Weigand, Institut for Microbiology, University of Veterinary Medicine Hannover, Foundation (TiHo)
  • Prof. Gabriele Köhler, Institut für Pathologie, Clinic Fulda, University Medicine Marburg

Founding

DFG

Further Research Projects

Project

Development of innovative multiplex diagnostic methods for the detection of viral and bacterial infections in laboratory animals based on highly immunogenic proteins

Objectives

The joint project has the overall objective of standardising and simplifying the assessment of the health status of laboratory animals. Therefore, we want to develop a test, which can simultaneously detect acute or early infections with bacterial and viral pathogens in mice.

Summary

The assessment of the health status of laboratory animals in Europe follows the recommendations of the FELASA (Federation of European Laboratory Animal Science Associations). Quarterly and yearly analyses are recommended against 24 pathogens to detect acute, persistent and already overcome bacterial and viral infections. Since the tests are not yet standardised, there is a high risk for false-positive and false-negative findings in practice. In addition, since for each pathogen a single test must be performed, high costs and work load arise. In this project we want to identify and express highly immunogenic proteins. Subsequently, the epitopes are isolated. The epitopes will then be used for a multiple, parallel serological test under standardise conditions for the identification of antibodies of FELASA-listed pathogens.

Project Manager

  • Prof. Christoph G. Baums
  • Prof. Ralf Hoffmann, Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), University Leipzig (Collaborative project)

Participating Associates

Sophie Kähl

Publications

Fingas F, Volke D, Hassert R, Fornefett J, Funk S, Baums CG & Hoffmann R. 2019. Sensitive and immunogen-specific serological detection of Rodentibacter pneumotropicus infections in mice. BMC Microbiology 19:43. doi: 10.1186/s12866-019-1417-7.

Michel V, Ulber C, Pöhle D, Köpke B, Engel K, Kaim U, Fawzy A, Funk S, Fornefett J, Baums CG, Eisenberg T. 2018. Clinical infection in house rats (Rattus rattus) caused by Streptobacillus notomytis. Antonie Van Leeuwenhoek. 111:1955-1966. doi: 10.1007/s10482-018-1085-x

Cooperation Partners

  • GVG Diagnostics GmbH, Leipzig
  • Prof. Thomas Vahlenkamp, Institute of Virology, Faculty of Veterinary Medicine, University Leipzig
  • Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), University Leipzig

Founding

EU (EFRE)

 

 

Project

Pathogen-Host interactions of Klebsiella pneumoniae in the bactericidal assay

Objectives

Investigation of the importance of adaptive IgM for the protective immunity development of piglets against the emerging pathogen Klebsiella pneumoniae and the relationship between metabolome and pathogen-host interaction in the blood.

Summary

Klebsiella pneumoniae is an important pathogen for pneumonia, septicaemia, abortion and mastitis pathogen, which can cause diseases in both animals and humans. Certain strains of K. pneumoniae belong to the so-called ESBL (extended spectrum beta-lactamase producing Enterobacteriaceae), which are resistant to a number of important antibiotics. A specific sequence type (ST25) of K. pneumoniae occurs in association with septicaemia in piglets as emerging pathogens in Great Britain and Australia. Currently, there are no data available for Germany. In general, there are less information about the immunity development and pathogen excretion in pigs. In this project, studies on the pathogen-host interaction of K. pneumonia in the porcine blood survivability test are planned. This serves to improve the understanding of the adaptive immune response of piglets and in particular to understand the importance of IgM for the protection against this bacteremia pathogen in an infected stock. Furthermore, the correlation between the host metabolom and predispositions for specific bacteremia are to be conducted in explorative investigations of ex vivo infected porcine and equine blood. The project aims to identify pathogen- and metabolom-dependent profiles in the plasma of bactericidal assays.

Project Manager

Karoline Rieckmann

Participating Associates

Cooperation Partners

  • PD Ingrid Vervuert, Institute of Animal Nutrition, Nutrition Diseases and Dietetics, Faculty of Veterinary Medicine, University Leipzig
  • PD Uwe Müller, Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig
  • Prof. Michael Kirschfink, Institute of Immunology, University Medical Centre Mannheim, Universität Heidelberg

Founding

Freundeskreis Tiermedizin der Veterinärmedizinischen Fakultät Leipzig e.V.

Project

Innovative AMP phage active compounds for the cost-effective treatment of infectious diseases of domestic animals as a biological and sustainable alternative to antibiotics.

Objectives

Investigation of the effect of selected antimicrobial peptides and modified phages on different bacterial strains

Summary

The use of antibiotics has led to a considerable selection of multidrug-resistant bacteria in both human and veterinary medicine. Considering the rapid spread of resistant bacteria, new agents are to be developed in cooperation with research group Hoffmann in a new, innovative approach. Therefore, bacteriophages should be used, which attack and lyse bacteria. In the genome of these phages sequences of Anti-microbial peptides with different mechanisms of action are to be integrated. As phages multiply in the animal’s bacteria, they only arise at the site of infection. The aim of the institute of Bacteriology and Mycology is to investigate the effects of AMPs and AMP phages in vivo and in vitro.

Project Manager

  • Prof. Christoph G. Baums
  • Prof. Ralf Hoffmann, Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), University Leipzig

Participating Associates

Ann-Kathrin Krieger

Cooperation Partners

  • Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), University Leipzig

Founding

EU (EFRE)

Project

Molecular- and cellular analysis of the host specificity of Streptococcus equi

Objectives

Identification of bacterial phenotypes, which are associated with the different host specificities of S. equi subspecies

Summary

In this project the interaction of S. equi with host proteins and respiratory epithelial cells is characterised. Furthermore, we target to identify bacterial virulence factors and to elucidate their function in persistent infections of the respiratory epithelium. The focus on the interaction of S. equi with equine and human bronchial epithel cells offers chances of collaboration within the faculty and university. The cytological and immunological investigations of the associated BALF of horses infected with S. equi allow a linkage of the in vitro results with these in vivo data. Confocal laser scanning microscopy (Core Unit CUL) as well as transmission- and scanning electrone microscopy is used to visualise adhesion, invasion and transmisson of streptococci.

Project Manager

Dr. René Bergmann

Cooperation Partners

  • Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University Leipzig
  • Medical Veterinary Clinic, Faculty of Veterinary Medicine, University Leipzig
  • Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig

Project

Studies on humoral and cellular immune reactions of dogs to persistent infections of the large intestine with brachyspirs for a better understanding of chronic diarrhoea

Objectives

In this project the immune reactions of dogs to brachspiral infections will be characterised and the importance of Brachyspira pilosicoli for different forms of chronic diarrhoea will be determined. A better understanding of the immune reactions in the intestinal tract of the dog allows a targeted treatment of chronic diarrhoea in the medium term.

Summary

Chronic diarrhoea (chronic diarrhoea, CD) occurs frequently in dogs. The cause is often not fully explained. A CD can become a heavy, long-lasting burden for the dog and thus also for the pet owner. Immunopathological processes play an important role in chronification and are probably associated with specific intestinal properties. Brachyspires, spirally wound gram-negative bacteria, have adapted to the large intestine as a habitat. Some Brachyspira species such as B. pilosicoli are important pathogens of colitis. New research suggests that these bacteria also cause diarrhoea in dogs. However, there are hardly any studies that show a connection between infection and chronic diarrhoea in dogs. In this project we want to characterise the immune reactions of dogs to brachyspiral infections and determine the importance of B. pilosicoli infections for the different forms of chronic diarrhoea. For the investigations we use samples from a clinical study of the Department for Small Animal and a Beagle pack of the Faculty of Veterinary Medicine naturally infected with B. pilosicoli. The medium-term goal is a targeted treatment of chronic diarrhoea through improved diagnostics.

Project Manager

  • Prof. Christoph G. Baums
  • Prof. Gottfried Alber, Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig
  • Prof. Romy Monika Heilmann, Department for small animal, Faculty of Veterinary Medicine, University Leipzig

Cooperation Partners

  • Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig
  • Department for small animal, Faculty of Veterinary Medicine, University Leipzig

Founding

Society for Cynological Research

 

Finished Research Projects

Project

Studies on the immunogenic and protective effect of selected Streptococcus suis antigens

Objectives

Streptococcus (S.) suis is one of the most important bacterial pathogens in modern pig husbandry. Prophylaxis is very difficult as no vaccine is approved in Europe. In many cases, whole groups of pigs are treated with antibiotics in order to control the stock problems with this pathogen. This project investigated the protective and immunogenic effect of a selected bacterial antigen in pigs. The focus of the work at the Institute of Immunology was on the investigation of antigen-specific leukocytes. With the help of single cell level studies including multiparameter flow cytometric analyses and ELISpot studies, cell types and their subtypes were characterized, the activation status of cells was determined and cytokine profiles were established. These investigations help within the project to investigate the efficacy of vaccines for the cellular response in pigs, a branch of the immune response that has often been neglected in vaccine development.

Project Manager

Prof. Christoph G. Baums

Participating Associates

Anna Seydel

Cooperation Partners

  • Prof. Gottfried Alber, Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig

Founding

IDT Biologika GmbH

 

Project

Development of innovative parallel diagnostic methods to detect viral and bacterial acute and past infections in experimental animals (Subproject 3 of this consortium)

Summary

Healthy mouse populations are an important prerequisite for medical research. The aim of this joint project is to establish tests that will enable better health monitoring of mouse populations. Bacterial pathogens, in particular Pasteurella pneumotropica, cause considerable problems in scientific investigations with mice. In cooperation with the partners, antigens of such pathogens are identified which are suitable for the development of highly specific and sensitive serological test methods (enzyme-linked immunosorbent assay, ELISA).

Project Manager

Prof. Christoph G. Baums

Participating Associates

Juliane Fornefett

Publications

Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Benga L, Grunwald T, Müller U, Schrödl W, Baums CG. 2018. Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain. BMC Microbiol. 8:45. doi: 10.1186/s12866-018-1186-8

Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Eisenberg T, Schrödl W, Grunwald T, Müller U, Baums CG. 2018. Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6 mice infected with Streptobacillus moniliformis. Microbes Infect. 20:101-110. doi: 10.1016/j.micinf.2017.10.001

Cooperation Partners

  • Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Centre for Biotechnology and Biomedicine (BBZ), University Leipzig
  • Institute of Virology, Faculty of Veterinary Medicine, University Leipzig
  • Fraunhofer Institute for Cell Therapy and Immunology IZI

Founding

EU (EFRE)

 

Project

Immunoglobulin proteases as immune evasion mechanism of Streptococcus suis

Summary

Streptococcus (S.) suis is an important invasive pathogen in pigs and humans that causes meningitis and septicaemia. We are investigating the interaction of this pathogen with the host and in particular with the humoral immune system. Of particular interest to us are mechanisms of the pathogen that lead to protection against the complement system. PhD Jana Seele and Prof. Christoph G. Baums were able to identify a highly specific IgM protease, IdeSsuis, of this pathogen. The project investigated the working hypothesis whether IgM cleavage by IdeSsuis represents a new complement evasion mechanism. In vitro and in vivo investigations are performed in the natural host pig to investigate the function of IdeSsuis in interaction with the immune system during the early phase of adaptive immunity. Together with the Swedish cooperation partner Prof. Ulrich von Pawel-Rammingen, a specific IgG protease of S. suis was identified and characterised. Furthermore, we also found a specific IgG protease in S. phocae subsp. phocae. S. phocae subsp. phocae infects marine mammals.

Project Manager

Prof. Christoph G. Baums

Participating Associate

Viktoria Rungelrath

Publications

Rungelrath V, Weiße C, Schütze N, Müller U, Meurer M, Rohde M, Seele J, Valentin-Weigand P, Kirschfink M, Beineke A, Schrödl W, Bergmann R, Baums CG. 2018. IgM cleavage by Streptococcus suis reduces IgM bound to the bacterial surface and is a novel complement evasion mechanism. Virulence. 9:1314-1337. doi: 10.1080/21505594.2018.1496778.

Rieckmann K, Seydel A, Szewczyk K, Klimke K, Rungelrath V, Baums CG. 2018. Streptococcus suis cps7: an emerging virulent sequence type (ST29) shows a distinct, IgM-determined pattern of bacterial survival in blood of piglets during the early adaptive immune response after weaning. Vet Res. 49(1):48. doi: 10.1186/s13567-018-0544-8

Rungelrath V, Wohlsein JC, Siebert U, Stott J, Prenger-Berninghoff E, von Pawel-Rammingen U, Valentin-Weigand P, Baums CG, Seele. 2017. Identification of a novel host-specific IgG protease in Streptococcus phocae subsp. phocae. Vet Microbiol. 201:42-48. doi: 10.1016/j.vetmic.2017.01.009

Cooperation Partners

  • Institute of Immunology, Faculty of Veterinary Medicine, University Leipzig
  • Prof. Ulrich von Pawel-Rammingen, Department of Medical Biochemistry and Biophysics, Umea University

Founding

Deutsche Forschungsgemeinschaft (DFG)

 

Project

Epidemiology and diagnosis of avian intestinal spirochetosis

Summary

Avian intestinal spirochetosis is caused by pathogenic species of the genus Brachyspira colonising the caecum and colon of poultry. The aim of this work is to determine the occurrence of the pathogenic Brachyspira species in laying hens in different keeping systems in Central Germany. Furthermore, the PCR- and MALDI-TOF-MS-based differentiation of the avian brachyspires is compared.

Project Manager

Prof. Christoph G. Baums

Participating Associate

Monika Harms

Publications

Harms M, Schmidt V, Heydel T, Hauptmann J, Ahlers C, Bergmann R, Baums CG. 2018. Differentiation of Brachyspira spp. isolated from laying hens using PCR-based methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Vet Diagn Invest. 30:545-553. doi: 10.1177/1040638718772319

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