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Grein Lab

 

Research

 

Bacterial Interference

The human gut is a highly complex ecosystem harboring hundreds to thousands of microbial species that coexist in this ecological niche in symbiotic or antagonistic relationships. This ecosystem can also be colonized by pathogenic bacteria and colonization has been shown to increase the risk of subsequent life-threatening infections. Therefore, decolonization is an effective tool to reduce the incidence of infections. Current decolonization strategies are often based on broad-spectrum antibiotics such as colistin, which not only affect pathogens but also the commensal microbiota. Additionally, these approaches bear the risk of selecting drug-resistant pathogens. Therefore, truly selective decolonization strategies are urgently needed. Within the DZIF research group “Bacterial Interference”, we exploit the human gut microbiome as a source for novel decolonization agents. Advanced cultivation techniques such as co-cultivation of several bacteria or supplying bacteria with growth factors, in particular under anaerobic conditions, are applied to exploit this resource for novel compounds. In an in vitro gut model, the colonization of the system by pathogenic bacteria is studied to analyze the direct antagonism of enteropathogenic bacteria and the commensal microbiota. Furthermore, the system is used to study the performance of different decolonization strategies. We aim at identifying optimal compositions of defined microbial communities for a selective and efficient decolonization.


Impact of antibiotics on the spatio-temporal organization of the cell wall biosynthesis machinery

The healthcare-associated pathogen Staphylococcus aureus causes a variety of infections, most notably soft tissue, skin, bone and bloodstream infections and is also the most common cause of postoperative wound infections. Antibiotics targeting the cell wall biosynthesis machinery of S. aureus are often the first choice in treating infections caused by this pathogen. How these antibiotics work on a cellular level is still incompletely understood. Within the transregional collaborative research center TRR 261 “ANTIBIOTIC CellMAP”, we study the impact of antibiotics on the spatio-temporal organization of the cell wall biosynthesis machinery together with the group of U. Kubitscheck (Institute of Physical and Theoretical Chemistry). Here, we analyze the downstream effects of different antibiotics on the organization of the membrane-bound cell wall biosynthesis machinery and how this contributes to drug potency. Antibiotic and target localizations are simultaneously monitored in S. aureus by advanced fluorescence microscopy while monitoring membrane integrity and cell viability. The effects of antibiotics with varying degree of membrane activity are compared. We will quantify interactions between components of the cell wall biosynthesis machinery and antibiotics in model membranes as a function of membrane properties.

 

Research examples

 

Research Example Damptomycin 

 

Funding

 

  • German Center for Infection Research (DZIF), TTU Healthcare-associated and Antibiotic-resistant bacterial Infections
  • DFG TRR261 Antibiotic CellMAP, project A11: Impact of antibiotics on the spatio-temporal organization of the cell wall biosynthesis machinery
  • National Institute of health (NIH), “Mechanisms and use of penicillin-binding protein inhibition to optimize cationic peptide anti-MRSA treatment“ (Co-PI)
  • Fonds der chemischen Industrie e.V.: “Sachkostenzuschuss für den Hochschullehrernachwuchs”
 

 

 

Team members

   

   

Fabian GreinFabian Grein
Junior Group Leader

Fabian Grein studied biology at the University of Bonn and gained his PhD on studies on the DsrMKJOP transmembrane complex in the purple sulfur bacterium Allochromatium vinosum in 2010. Following his PhD studies, he became a PostDoctoral fellow at the Institute for Technology, Chemistry and Biology (ITQB), New University of Lisbon, Portugal, working on sulfur metabolism in Desulfovibrio vulgaris. He then returned to Germany and joined the Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, working on the DFG funded project “Antibiotics with pleiotrophic activities: Daptomycin and amphiphilic glycopeptides”. In 2015, he became group leader of the DZIF Junior Research Group “Anti-staphylococcal Targets” at the inter-faculty Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn.

room 40
phone: +49(0)228 73 5247

e-mail

 

 

PlatzhalterDennis Hasenklever
Master student


room 63
phone: +49(0)228 73 2112

e-mail

 

 

Nils JeldenNils Jelden
PhD student

room 63

phone: +49(0)228 73 2112

e-mail

Benjamin WinnerlingBenjamin Winnerling
PhD student

room 20

phone: +49(0)228 73 2113

e-mail

 

 

Jan-Samuel PulsJan-Samuel Puls
PhD student


room 20
phone: +49(0)228 73 2113

e-mail

 

 

Thomas FließwasserThomas Fließwasser
Postdoctoral Researcher


 

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