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AG Patenge


Contact

Dr. rer. nat.

Nadja Patenge 

  • Wissenschaftlerin
    am Institut für Medizinische Mikrobiologie, Virologie und Hygiene

+49 (0) 381 494 5916
+49 (0) 381 494 5967

+49 (0) 381 494 5902 

nadja.patenge{bei}med.uni-rostock.de


Büro

Raum: 264

Universitätsmedizin Rostock
IMIKRO
Schillingallee 70
D-18057 Rostock

Sekretariat

Gudrun Riedel

  • Sekretärin
    am Institut für Medizinische Mikrobiologie, Virologie und Hygiene

+49 (0) 381 494 5919
+49 (0) 381 494 5925

gudrun.riedel{bei}med.uni-rostock.de

Raum: 112, EG

Publikationen

AG Patenge

Leiterin der AG Patenge

AG Kreikemeyer

Mitarbeiterin der AG Kreikemeyer

Main Topics

Small non-coding regulatory RNAs in Streptococcus pyogenes

S. pyogenes is a strictly human pathogen. It is responsible for a variety of human diseases, ranging from mild superficial infections (pharyngitis, impetigus) to invasive, life-threatening diseases (necrotizing fasciitis, streptococcal toxic shock syndrome). S. pyogenes is able to colonize different body surfaces in the human host and distinct strains exhibit considerable differences in virulence. The required adaption to the conditions at various host sites is achieved by a tightly controlled expression of streptococcal virulence factor genes. Beside protein-mediated transcriptional regulation of gene expression, bacteria possess small regulatory RNAs (sRNAs), which modulate gene expression through RNA-RNA or RNA-protein interaction.

In previous studies, we screened the genome of S. pyogenes for sRNA genes using bioinformatics approaches and gene-expression analysis tools, identifying more than fifty potential sRNA candidate genes. Now, we are interested in the regulatory mechanisms of the individual sRNAs and in the role of these molecules in streptococcal virulence. We constructed mutant strains, lacking or overexpressing the respective sRNA genes. The strains were compared to the parental strains in vitro and in vivo. For a deeper understanding of the sRNA function, it is necessary to identify molecular sRNA targets. Therefore, we use bioinformatics prediction programs and transcriptomic as well as proteomic approaches.

In this project we are collaborating with Georg Fuellen (IBIMA/ Rostock), Stefan Mikkat (Proteome Center Rostock/ Rostock), and Joern Kalinowski (CeBiTec, Bielefeld).


Dr. Nadja Patenge, Afsaneh Khani, Roberto Pappesch, Nicole Popp, Maja Wittmann, Aleksandra Wisniewska-Kucper

Identification of RNA-binding proteins in Streptococcus pyogenes

S. pyogenes uses sRNAs for the regulation of virulence gene expression. In many bacterial species, RNA-binding proteins play a role in the function of sRNAs as molecular chaperones or as protein targets. Among those, Hfq is the best-characterized sRNA-binding protein. Hfq has been initially discovered in Escherichia coli, but it is involved in sRNA folding as well as in facilitating sRNA-mRNA interaction in many bacterial species. However, hfq is not present in S. pyogenes. We are aiming at identifying sRNA-binding proteins by two different approaches: i) heterologous expression of putative RNA helicase genes, purification of the recombinant protein, and in vitro sRNA-protein binding studies; ii) aptamer-mediated affinity co-purification of sRNA-binding proteins from S. pyogenes cell extracts, followed by mass spectrometry.

For surface plasmon resonance analyses of RNA-protein interaction we will collaborate with Sonja Oehmcke-Hecht in our department (IMIKRO, Rostock). Mass spectrometry analyses will be performed by Stefan Mikkat (Proteome Center Rostock/ Rostock).


Dr. Nadja Patenge, Nicole Dehn

Peptide nucleic acid (PNA)-antisense technology

Streptococcal infections represent a considerable global burden on individual patients and human society. To date, S. pyogenes is still susceptible towards penicillin. However, some patients exhibit penicillin allergies. Moreover, in pharyngitis, penicillin treatment failure has been observed, a phenomenon that might be caused by intracellularly residing S. pyogenes. Streptococcal resistance towards macrolides, which are used as an alternative treatment option, has been rising in recent years. Taken together, these facts make it mandatory to develop novel therapeutic strategies.    

PNAs are synthetic molecules similar to DNA and RNA featuring the purine and pyrimidine bases covalently linked to a peptide backbone. PNAs can interact with DNA and RNA in a sequence-specific manner. The molecules are very stable and binding to DNA and RNA is very strong. Therefore, PNAs are promising candidates for antisense-treatment of bacterial infections. We were able to show that PNAs specific for streptococcal gene sequences, if fused to cell penetrating peptides (CPPs), could inhibit growth of S. pyogenes. CPP-fusion will also allow targeting of intracellular bacteria. Currently, we are studying the effect of different combinations of CPP and target sequences. CPP-PNAs, which inhibit streptococcal growth in vitro, are being evaluated in a Galleria mellonella insect infection model.

In this project we are collaborating with Anette Jacob (Peps4LS GmbH, Heidelberg).


Dr. Nadja Patenge, Roberto Pappesch, Sebastian Sarodnik

Oxidative Stress during Infection

In the course of an infection, bacteria and host cells are exposed to oxidative stress generated by the immune response of the host. We are studying whether oxidative stress resistance in bacteria influences virulence. Additionally, we are interested in the degree of host tissue damage caused by oxidative stress during infection.

Employing a mouse infection model, we are studying the virulence of S. pyogenes mutants, which are either sensitive or resistant towards oxidative stress in comparison to the parental strains. From host tissue samples collected throughout infection, we are detecting stress-induced damage in bacterial DNA and in host mitochondrial DNA using quantitative PCR.

In an independent approach, we are investigating the consequences of oxidative stress-inducing mitochondrial mutations in ageing mice. Therefore, DNA-damage is measured in different mouse tissues, comparing young and old animals. This project is conducted in collaboration with Saleh Ibrahim (UKSH, Lübeck).


Dr. Nadja Patenge, Jana Normann, Aleksandra Wisniewska-Kucper

Team

Group leader

Dr. rer. nat.

Nadja Patenge 

  • Wissenschaftlerin
    am Institut für Medizinische Mikrobiologie, Virologie und Hygiene

+49 (0) 381 494 5916
+49 (0) 381 494 5967

+49 (0) 381 494 5902 

nadja.patenge{bei}med.uni-rostock.de


Büro

Raum: 264

Universitätsmedizin Rostock
IMIKRO
Schillingallee 70
D-18057 Rostock

Sekretariat

Gudrun Riedel

  • Sekretärin
    am Institut für Medizinische Mikrobiologie, Virologie und Hygiene

+49 (0) 381 494 5919
+49 (0) 381 494 5925

gudrun.riedel{bei}med.uni-rostock.de

Raum: 112, EG

Publikationen

AG Patenge

Leiterin der AG Patenge

AG Kreikemeyer

Mitarbeiterin der AG Kreikemeyer

Team

MSc

Gina Barkowsky

  • Phd-Student
    am Institut für Medizinische Mikrobiologie, Virologie und Hygine

+49 (0) 381 494  5920
+49 (0) 381 494  5794
+49 (0) 381 494  5902

gina.barkowsky{bei}med.uni-rostock.de

Büro:    260,  1. OG

MSc

Afsaneh Khani

  • Phd-Studentin
    am Institut für Medizinische Mikrobiologie, Virologie und Hygine

+49 (0) 381 494  5939
+49 (0) 381 494  5794
+49 (0) 381 494 5902

afsaneh.khani{bei}med.uni-rostock.de

Büro:    265A,  1. OG

MSc

Roberto Pappesch

  • Phd-Student
    am Institut für Medizinische Mikrobiologie, Virologie und Hygine

+49 (0) 381 494  5939
+49 (0) 381 494  5794
 +49 (0) 381 494 5902

roberto.pappesch{bei}gmail.com

Büro:    265A,  1. OG

Mirijam Schäfer

Master student

+49 (0) 381 494 5939

Judith Hüttner

Md student

+49 (0) 381 494 5939

Technical assistant

Jana Normann

  • Medizinisch-technische Assistentin in der Forschung
    am Institut für Medizinische Mikrobiologie, Virologie und Hygiene

+49 (0) 381 494 5799
+49 (0) 381 494 5794
+49 (0) 381 494 5795
+49 (0) 381 494 5902

jana.normann{bei}med.uni-rostock.de

Labor: 004A, KG
Büro:     101, EG

Alumni