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Institute of Molecular Pathogenesis (IMP)

Working group Pathogenomics

An organism’s genome contains essential information that can be exploited to answer a wide array of biological questions concerning phylogeny, outbreak dynamics and epidemiology as well as metabolic diversity, pathogenicity and virulence, to name a few. Changes in the genome of a bacterial strain due to individual gene loss, gene acquisition and gene mutation can, for example, profoundly affect its ability to survive in a specific habitat, to infect a certain cell type or to metabolize particular substrates. The comparison of many genomes from related strains or species, e.g., by means of genome wide association studies, can aid in identifying the genetic basis for these phenotypic traits. 

Main Research Topics

Our main research interest is to detect correlations between a zoonotic pathogen’s genome sequence and its ability to colonize a host and replicate in it and to characterize these at the organismic, cellular and molecular levels. Here, we mainly focus on two organisms, Escherichia coli and Coxiella burnetii, which utilize different patterns/strategies to establish genome dynamics.

With about 2,000 gene families in its core genome and close to 90,000 in its still quite open pan genome, E. coli exhibits remarkable genomic and phenotypic variation. This genetic plasticity is mainly driven by widespread horizontal gene transfer and strongly contributes to defining the many pathovars that have been described so far. One important pathovar is Shiga toxin producing E. coli (STEC), which can cause outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) in humans. Human pathogenic STEC are also referred to as enterohemorrhagic E. coli (EHEC). Cattle and other ruminants serve as natural reservoir hosts of STEC strains. We recently showed that this may also hold for an EHEC/enteroaggregative hybrid strain of serotype O104:H4, the cause of an unprecedented large HUS outbreak which struck Germany in 2011. Understanding the factors crucial for STEC survival and colonization in ruminants will aid in designing new intervention strategies to prevent human disease. A longitudinal study investigating the shedding of STEC from cattle revealed that some strains persisted for longer periods of time, while others were detected only sporadically. Persisting strains can serve as gene reservoirs that supply other E. coli strains with virulence factors, thereby generating new outbreak strains. By analyzing representative genes of the respective core and accessory genomes, we try to define the underlying genetic patterns that distinguish these persistent from sporadically colonizing STEC isolates.

Coxiella burnetii, an obligate intracellular pathogen, is the causative agent of the zoonotic disease Q fever, which either presents as an acute, usually self-limiting flu-like disease or, more rarely, as a chronic endocarditis or vascular illness. Genome evolution within the genus involves genome rearrangement, differential formation of pseudogenes and insertion element expansion and there are correlations between pathotype and genome content. Our research interest is to identify factors, either pathogen- or host cell-encoded, that contribute to host cell specificity and disease etiopathology.

These research topics are addressed experimentally using methods from Next Generation Sequencing, Molecular Biology, Genetics and Genome Engineering, Microbiology, Cell Biology and Immunology.