This project focuses on severe acute infections caused by Gram-positive bacteria: group A, B, and G streptococci (GAS; GBS, and GGS) and Staphylococcus aureus. These microorganisms are associated with a variety of diseases ranging from superficial skin and throat infections to life-threatening sepsis, toxic shock syndrome and necrotizing soft tissue infections (NSTIs). The latter are rapidly progressing infections associated with high mortality and morbidity. In this project we will apply tissue engineering to generate in vitro skin, which will allow us to study bacterial persistence and resistance phenotypes at the tissue site, including phenotypic switches of the bacteria and biofilm formation. Further, we are aiming to identify potential virulence mechanisms, therapy targets, and host pathways contributing to the severity of infection.

Project start: Fall 2018 | Main experimentators: Katharina E. Folz; Vartika Singh | Funding:  t.b.d.

This research is performed with a number of international and national collaborators, including: Anna Norrby-Teglund (Karolinska Institutet, Stockholm, Sweden), Lakshmi Rajagopal (Seattle Children's Research Institute, Seattle, WA, USA), Bernd Kreikemeyer (University of Rostock, Rostock, Germany).

Neutrophils are the major leukocyte component of the blood and the first recruited responders at the site of bacterial infection. Three distinct mechanisms to fight an infection are described: phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Critical components of all these processes are granule effector molecules, including proteolytic enzymes and antimicrobial peptides. Streptococcal species have evolved a distinct repertoire of protein cytotoxins that interfere with crucial neutrophil functions. In this project, we aim to: (i) identify potential human neutrophil receptors which are targeted by streptococcal toxins, (ii) characterize the interaction and the resulting consequences, and (iii) identify natural and therapeutic neutralizing agents to be able to prevent excessive neutrophil activation and subsequent tissue pathology.

Project start: Nov 2022 | Main experimentator: Anna Riegner | Funding:  DFG (German Research Foundation)

Project within the Priority Programme “Emergent Functions of Bacterial Multicellularity” (SPP 2389)

Streptococci cause a wide range of diseases including necrotizing skin and soft tissue infections. Until recently, biofilms were not recognized as a potential problem in streptococcal infections, as they are typically linked to chronic infections or associated with foreign devices. We observed “thick” biofilm communities in the skin tissue biopsies of several patients infected with streptococcal species. Moreover, these biofilm communities are of heterogenic multicellular nature. Confocal laser scanning microscopy (CLSM) analyses revealed that streptococcal biofilms consist of two subpopulations. First population, a potentially metabolically inactive, is permeable for cytosolic probing, while the second is not. Our data indicate that the second population is versatile in nature. It can remain within the biofilm structure or disperses to the surrounding tissue. In this project, we aim to metabolically profile these two distinct populations and mechanistically analyze the signaling.

Project start: Nov. 2022 | Main experimentators: Katharina E. Folz & Constantin Klein | Funding:  DFG (German Research Foundation)

This research is performed in close collaboration with Michael Lalk´s group (Institute of Biochemistry; Greifswald), international collaborators: Bård R. Kittang, Oddvar Oppegaard, Steinar Skrede (Haukeland University Hospital, Bergen, Norway), Anna Norrby-Teglund (Karolinska Institutet, Stockholm, Sweden), and national collaborators, including Sylvio Redanz (University Medicine Münster) and partners within the SPP 2389 priority program.

Streptococcus pyogenes (group A streptococci; GAS) is an exclusively human Gram-positive pathogen and the main causative agent of monomicrobial necrotizing soft tissue infections (NSTIs). NSTIs are rapidly progressing infections of any layer of the skin or soft tissue and are associated with significant morbidity and mortality. To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Our results indicate that GAS heterogeneity is characterized by a divers virulence factor expression profile as a result of a tissue passage. Infections with distinct GAS populations lead to failed immuno-detection and bacteria-mediated suppression of immune responses in the human host. The immuno-suppressive state provides a beneficial environment for bacterial proliferation and dissemination through the tissue resulting in excessive tissue pathology and severe outcome of infection.

Project start: Fall 2024 | Main experimentators: Katharina E. Folz & Vartika Singh

Prosthetic joint infections (PJIs) are severe complications in orthopedic surgery, which necessitate a complete eradication of all bacteria. The focus in PJI treatment is based on the microbiological culture results and does not consider patient’s individual immune status. All data indicate that a persistent inflammation and resulting massive infiltration of a plethora of immune cells leads to an exhaustion of these cells and subsequently allows bacterial settlement. This project aims to decipher the pathomechnism underlying PJIs as a consequence of local metal exposure.

Project start: Fall 2021 | Main experimentator: - | Funding:  t.b.a.

This research is performed in close collaboration with Janosch Schoon and Georgi I. Wassilew (University Medicine Greifswald).