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Projects

Our projects cover several aspects of the problem that is posed by the growing antibiotic resistance in bacteria.

 

Kinases and the antibiotic activity against Staphylococcus aureus

 DFG Logo

 

 Staphylococcus aureus, especially the methicillin resistant S. aureus (MRSA), is one of the most prominent infectious agents and causes mainly nosocomial disease. Infections with MRSA strains are treated with vancomycin or newer chemotherapeutics like synercid, daptomycin and linezolid. We have characterized a strain pair showing intermediate resistance to vancomycin (VISA) and shown that mutations in a regulatory two component system (WalRK) and inactivation of a membrane protein, decreased cross linking of the cell wall as well as increased cell wall biosynthesis lead to this phenotype. The cell envelope composition of a laboratory mutant that displays a high level of vancomycin and daptomycin resistance is currently being analysed in detail. Here two of the kinases involved in stress response (VraS) and cell wall biosynthesis (WalK) carry mutations. In order to study the properties of these kinases in detail we are reconstructing the mutations in vivo and have installed in vitro systems for both kinases. Currently we test kinase activity under different conditions, evaluate possible inhibitors and look for the signals that stimulate kinase activity. 

 

 

Evolution and dissemination of antibiotic resistance

 HyReKA logoDFG Logo

Additionally, we are interested in the relationship between environmental stress and the development and dissemination of antibiotic resistance. Possible mechanisms that confer slow evolution of resistance are the mobilisation of IS-elements, transposons etc. or point mutations, which may be caused by an increased mutation frequency. For example, a high number of IS elements is present in two of the strains described above and we could show that these elements are able to cause reversible formation of strains with increased resistance to antibiotics.
Antibiotic-resistant intestinal bacteria enter the environment through the waste water system and sewage water treatment plants which have become a hot spot of horizontal resistance gene transfer. Contact with these resistant bacteria, for example via surface water can lead to re-colonisation of the human intestine. Infections by these bacteria  – which in most cases are urinary tract infections or sepsis that occur upon hospitalisation – are difficult to treat. We participate in HyReKA, which is a BMBF funded project that examines the spread of clinically resistant bacteria and antibiotics through the waste water from hospitals, municipal areas, airports and agricultural facilities into waste water treatment plants and their effluents. A special concern are pathogens with resistance against last resort antibiotics.

 

Novel antibiotics and lantibiotics

 Infect Control 2020   DFG Logo

 

Lantibiotics (lanthionine containing antibiotics) are ribosomally synthesized peptides with antibacterial activity. The rare amino acids, e. g. the thioether forming lanthionines, are synthesized by characteristic modification enzymes that are encoded in the vicinity of the structural genes in biosynthetic gene clusters. Most lantibiotics described so far are produced by and active against Gram-positive bacteria, for example mersacidin, lichenicidin and pseudomycoicidin (DFG FOR854). In the last years we have also included non-lantibiotic compounds into our studies (DrugBioTune in the InfectControl 2020 program).

 

New typing methods

  DZIF              

Antibiotic resistant bacteria that cause nosocomial infections present a considerable health care burden. For epidemic surveillance, the isolates have to be typed. However, the conventional molecular genetic methods are labor-intensive and/or expensive. Since no cost-efficient method is available, prospective typing is generally not performed. Within a project funded by the DZIF we have evaluated MALDI-TOF mass spectrometry for strain specific peak shifts which can be exploited for detection of clonal lineages or resistance traits.

 

 

The impact of bacterial activity on decay and fossilization of arthropods

 FOR 2685   DFG Logo

 

The objective of this project is to improve the general understanding of decay and fossilization processes in context with microbial activity. Insights into evolution and phylogeny of arthropods are derived from excellently preserved fossils, which were formed by a complex sequence of biological, chemical and geological processes that starts immediately post mortem. Between death and embedding, decay (aerobic) and putrefaction (anaerobic), catalyzed by microorganisms that originate from the gut flora of the arthropod and its environment, may lead to a partial loss of characteristic features important for phylogenetic interpretations.  In addition to the decay of organisms, bacteria have also been shown to contribute to the formation of fossils, by synthesizing biofilms which later fossilize by precipitation of minerals and yield casts or pseudomorphs of the hard and fine tissues of the carcass. Also the precipitation of minerals might be a product of bacterial activity. The experiments will test the influence of bacteria on the decay of crustaceans.

 

Poster of current projects

 

 IS256 promotes formation of unstable antibiotic resistant small colony variants in Staphylococcus aureus

The role of the VraS histidine kinase in vancomycin resistance in Staphylococcus aureus

Development of MALDI-TOF MS software for detection of Staphylococcus aureus lineages

 

 

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