Nikolai Siemens group - "Infectious Diseases"

Group leader

Nikolai Siemens

Dr. rer. nat., Professor
Nikolai received his Diploma and Dr. rer. nat. degrees from University of Rostock (Germany) in 2009 and 2012, respectively. He completed postdoctoral studies at the Center for Infectious Medicine, Karolinska Institutet (Stockholm, Sweden) in 2016. Nikolai established his own laboratory at the Department of Molecular Genetics and Infection Biology, University of Greifswald in 2017. In 2021, he was appointed professor in molecular genetics of infections. His research focuses on severe invasive infections caused by Gram-positive bacteria.

Contact:

Department of Molecular Genetics and Infection Biology
University of Greifswald
Felix-Hausdorff-Straße 8 | 17489 Greifswald, Germany
Phone: +49 3834 420 5711 | nikolai.siemensuni-greifswaldde

Group members

Anna Riegner

PhD student
Anna received her Master degree in Molecular Biology and Physiology from University of Greifswald. In her doctoral studies she focuses on streptococci and human neutrophils interplay and how these actions are contributing to the severity of infection.

 

Contact:
Phone +49 3834 420 5716
anna.riegner@uni-greifswald.de

Janine Neufend

PhD student
Janine received her Master degree in Molecular Biology and Physiology from University of Greifswald. In her doctoral studies she analyzes the heterogeneity of beta-hemolytic streptococci in different infection scenarios with a particular focus on biofilms.

 

Contact:
Phone +49 3834 420 5716
janine.neufend@uni-greifswald.de

Katharina E. Folz

PhD student
Katharina received her Bachelor and Master degrees in Biochemistry from the University of Greifswald. In her studies she analyzes immune responses in bacterial infections. Furthermore, she is interested in evasion strategies of group A, C, and G streptococci in NSTIs.

 

Contact:
Phone +49 3834 420 5751
katharina.folzstud.uni-greifswaldde

Technical assistant

Karsta Barnekow

Contact:
Phone +49 3834 420 5722
karsta.barnekow@uni-greifswald.de

Current B.Sc. and M.Sc. students

Debby Schubert (B.Sc. student)
debby.schubert@stud.uni-greifswald.de

Carolina Wieters (B.Sc. student)
carolina.wieters@stud.uni-greifswald.de

 

Former group members

PhD students and scientists

Dr. Lea A. Tölken (2020-2024)
Dr. Patience Shumba (2018-2022)
Dr. Surabhi Surabhi (2017-2021)
Dr. Fabian Cuypers (2017-2021)
Antje D. Paulikat (2020-2021)
Lana H. Jachmann (2020-2021)
Sebastian B. Skorka (2017-2019)

MSc and BSc students

Emily Friedrich (MSc student, 2024)
Max Sittner (MSc student, 2024)
Celina Würner (MSc student, 2022)
Felicitas Hubert (BSc student, 2021)
Charlotte Coenders (MSc student, 2020)
Stephan M. Schneiders (MSc student, 2017-2018)
Björn Klabunde (MSc student, 2017-2018)


Projects

Resistance and persistence strategies by Gram-positive bacteria in necrotizing skin and soft tissue infections

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 experimentator: Katharina E. Folz | 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-Streptococci-Interplay

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: Fall 2022 | Main experimentator: Anna Riegner | Funding:  DFG (German Research Foundation)

Stay tuned. Project begins Nov 2022

Biofilm heterogeneity in streptococcal infections

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 experimentator: Janine Neufend | Funding:  DFG (German Research Foundation)

This research will be 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.

 

Immune response manipulation by streptococci

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 2021 | Main experimentator: Katharina E. Folz | Funding:  t.b.a.

Metal-mediated immunosuppressive effects in peri-implant bacterial infections

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).

Key collaborators

International:

  • Anna Norrby-Teglund, Karolinska Institutet, Sweden
  • Steinar Skrede, University of Bergen, Norway
  • Lakshmi Rajagopal, University of Washington, USA
  • Natalia Korotkova, University of Kentucky, USA
  • John McCormick, Western University, Canada

National:

  • Marcus Fulde, FU Berlin
  • Sonja Oehmcke-Hecht, University Medicine Rostock
  • Bernd Kreikemeyer, University Medicine Rostock
  • Sylvio Redanz, University of Münster
     

Local:

  • Michael Lalk, University of Greifswald
  • Janosch Schoon, University Medicine Greifswald
  • Georgi I. Wassilew, University Medicine Greifswald
  • Stefan Finke, FLI Island Riems

C_FunGene:

  • Sven Hammerschmidt, University of Greifswald
  • Uwe Völker, University Medicine Greifswald
  • Katharina Hoff, University of Greifswald
     

Selected publications

2024

Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes. Tölken LA, Paulikat AD, Jachmann LH, Reder A, Gesell Salazar M, Palma Medina LM, Michalik S, Völker U, Svensson M, Norrby-Teglund A, Hoff KJ, Lammers M, Siemens N. Journal of Biomedical Science. 2024 Feb 27;31(1):26. doi: 10.1186/s12929-024-01014-9.

Cobalt and chromium ions impair macrophage response to Staphylococcus aureus infection. Tölken LA, Wassilew GI, Grolimund D, Weitkamp T, Hesse B, Rakow A, Siemens N, Schoon J. ACS Biomaterials Science & Engineering.  2024. Jan 8;10(1):563-574. doi: https://doi.org/10.1021/acsbiomaterials.3c01031.

Prior to 2024 (selected)

Streptococcus pyogenes reversibly abrogates SpeB secretion in response to neutrophil-derived reactive agents in tissue infections. Shumba P, Sura T, Moll K, Chakrakodi B, Tölken LA, Hoßmann J, Hoff KJ, Hyldegaard O, Nekludov M, Svensson M, Arnell P, Skrede S, INFECT Study Group, Norrby-Teglund A, and Siemens N. Journal of Biomedical Science. 2023 Jul 10;30(1):52. doi: 10.1186/s12929-023-00947-x.

Streptococcus pneumoniae Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4+ T cells via Pneumolysin. Paulikat AD, Tölken LA, Jachmann LH, Burchhardt G, Hammerschmidt S, and Siemens N. The Journal of Innate Immunity. 2022 Mar 4:1-12. doi: 10.1159/000522339.

The procoagulant activity of blood and microvesicles is disturbed by pneumococcal pneumolysin, which interacts with coagulation factors. Oehmcke-Hecht S, Maletzki C, Surabhi S, Siemens N, Khaimov V, John LM, Peter SM, Hammerschmidt S, Kreikemeyer B. The Journal of Innate Immunity. 2022 Jul 15:1-17. doi: 10.1159/000525479.

Bronchial Epithelial Cells Accumulate Citrate Intracellularly in Response to Pneumococcal Hydrogen Peroxide. Surabhi S, Jachmann LH, Lalk M, Hammerschmidt S, Methling K, Siemens N. ACS Infectious Diseases. 2021 Oct 8. doi: 10.1021/acsinfecdis.1c00372.

Hydrogen Peroxide is Crucial for NLRP3 Inflammasome-Mediated IL-1β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells. Surabhi S, Jachmann LH, Shumba P, Burchhardt G, Hammerschmidt S, Siemens N. The Journal of Innate Immunity. 2021. Aug 6:1-15. doi: 10.1159/000517855

Pathogenic Mechanisms of Streptococcal Necrotizing Soft Tissue Infections. Siemens N, Snäll J, Svensson M, Norrby-Teglund A. Advances in Experimental Medicine and Biology. 2020;1294:127-150. doi: 10.1007/978-3-030-57616-5_9.

Adenosine Triphosphate Neutralizes Pneumolysin-induced Neutrophil Activation. Cuypers F, Klabunde B, Gesell Salazar M, Surabhi S, Skorka SB, Burchhardt G, Michalik S, Thiele T, Rohde M, Völker U, Hammerschmidt S, Siemens N. The Journal of Infectious Diseases. 2020. Oct 13;222(10):1702-1712. doi: 10.1093/infdis/jiaa277.

Is it time to reconsider the group A streptococcal rheumatogenic concept? Norrby-Teglund A and Siemens N. Clinical Infectious Diseases. 2020 Mar 17;70(7):1461-1462. doi: 10.1093/cid/ciz427.

Shocking superantigens promote establishment of bacterial infection. Siemens N and Norrby-Teglund A. Proc Natl Acad Sci USA. 2017 Sep 19;114(38):10000-10002. doi: 10.1073/pnas.1713451114. Epub 2017 Sep 12.

Biofilm in group A streptococcal necrotizing soft tissue infections. Siemens N, Chakrakodi B, Shambat SM, Morgan M, Bergsten H, Hyldegaard O, Skrede S, Arnell P, Madsen MB, Johansson L; INFECT Study Group, Juarez J, Bosnjak L, Mörgelin M, Svensson M, Norrby-Teglund A. Journal of Clinical Investigation Insight.  2016 Jul 7;1(10):e87882. doi: 10.1172/jci.insight.87882.

Phosphoglycerate kinase – a novel streptococcal factor involved in neutrophil activation and degranulation. Uhlmann J, Siemens N, Kai-Larsen Y, Fiedler T, Bergman P, Johansson L, Norrby-Teglund A. The Journal of Infectious Diseases. 2016 Dec 15;214(12):1876-1883. doi: 10.1093/infdis/jiw450. Epub 2016 Sep 28.

A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains. Mairpady Shambat S, Siemens N, Monk IR, Mohan DB, Mukundan S, Krishnan KC, Prabhakara S, Snäll J, Kearns A, Vandenesch F, Svensson M, Kotb M, Gopal B, Arakere G, Norrby-Teglund A. Scientific Reports. 2016 Aug 11;6:31360. doi: 10.1038/srep31360.

Genetic Architecture of Group A Streptococcal Necrotizing Soft Tissue Infections in the Mouse. Chella Krishnan K, Mukundan S, Alagarsamy J, Hur J, Nookala S, Siemens N, Svensson M, Hyldegaard O, Norrby-Teglund A, Kotb M. PLoS Pathogens. 2016 Jul 11;12(7):e1005732. doi: 10.1371/journal.ppat.1005732. eCollection 2016 Jul.


Open positions

We always want to get in touch with talented and highly motivated potential co-workers interested in translational research aimed at understanding the mechanisms of highly lethal infectious diseases. If you are interested in doing research within our group, as a degree project, please contact the group leader Nikolai Siemens.

PhD student