Navigation and service

JRG 1: Microbial Genomics

Project Leader:
Torsten Semmler

Staff

Dr. Ramani Baddam
Temesgen Dadi, M.Sc.
Barbara Moriel, M.Sc.
Lennard Epping, B.Sc.

Subject

At the research group „Microbial Genomics“ we focus on the mechanisms of the evolution and spread of bacterial pathogens in humans as well as in animals. Most methods that we use are genomic approaches that are combined with phenotypic analyses to understand the virulence, transmission and host-interactions of the bacteria.

An important theme of our research activities is the understanding of Anti-Microbial Resistance (AMR) which is one of the most essential evolutionary forces in the development of the bacteria in the presence.

The group is following two approaches to increase the knowledge, one is to investigate a wide variety of human and animal pathogens to study and compare the diversity of mechanisms that are responsible for the virulence of a strain and its ability to infect various hosts. In this context we also characterize the whole population of a species to identify certain evolutionary successful phylogenetic groups or groups that are characterized by an increase of their pathogenicity and/or an extended antimicrobial resistance and try to find the molecular source for this. We identify orthologous genes, present in all members of the population which will be used to compare the strains and their shared molecular characteristics and genes that are accessory for example responsible for interaction with specific hosts, or for specific pathogenic mechanisms. We often find associations here. For example in Escherichia coli strains of the phylogenetic group B2 are more likely associated with pathogenicity and show on the genomic level a decreased diversity together with an increased recombination rate. Another example where we look into the details of the genomes of a whole population is the emergence of drug resistant strains and their global spread. This enables us to track how resistant strains like Extended-spectrum beta-lactamases E.coli (ESBL) and Methicillin-resistant Staphylococcus aureus (MRSA) are on the rise and what are the mechanisms behind this trend.

On the other hand we also analyze and compare very closely related strains of one species. Such comparisons allow us to track the microevolution within evolutionary successful lineages and ancient origins of a species. For example we are able to determine the genomic factors that are responsible for the emergence and worldwide spread of E.coli ST131, ST648, ST410 focusing their high zoonotic potential as well as their increased AMR prevalence. We also get an insight into the E.coli ST10 group where the evolutionary origin of E.coli is assumed and which contains commensal strains as well as pathogenic ones with the same evolutionary background giving us the opportunity to find the driving forces for the transformation of commensals into pathogens. Combined with analyses of metabolic pathways this will make it possible to identify potential vaccination or drug targets. In Methicillin-resistant Staphylococcus pseudintermedius (MRSP), which is another typical nosocomial pathogen and an evolutionary very young species the absolutely predominant clone is ST71. Based on a high resolution comparison of the whole genomes, distinct factors can be identified that differentiates this clone from the rest of the population and may be the key to success for this linage.

Infectious diseases are still a global and local threat. On the one hand the causing bacteria are evolving very quickly and on the other hand these bacteria can be resistant to almost all antibiotics. This can have fatal consequences, particularly in developing countries. Mechanisms of adaptations on the pathogen side as well as on the host side and their interaction are supposed to play an important role in the spread of infectious agents. In the case of Enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea, it could be shown on the basis of whole genome analyses that although the different global lineages have clade specific distinct toxin profiles and colonization factors they might harbor chromosome and plasmid combinations that optimize fitness and transmissibility.

Infectious events, especially in the gut as well as their antibiotic treatment, which is mostly oral, have a huge impact on the human microbiome. While it is only very little known about the mechanisms that lead to the functional consequences in an event of disruption of the equilibrium in the composition of the microbiome in the gut, the variety of effects to the health of the host is impressive. But it is not only humans that have to be considered. The gut of animals, production as well as wildlife, is an important reservoir for zoonotic pathogens and Anti-Microbial Resistances which have influence on public health either direct or via the environment.

We therefore also focus on the development of new algorithms for species identification and a quantification of the resistome and virulome in shotgun metagenomics datasets and their application in medical and veterinary setups.

Prevalence of ESBL in the E.coli population based on the data of 7766 strains from different epidemiological background. Source: RKI and Prof. Dr. Christa Ewers Prevalence of ESBL in the E.coli population based on the data of 7766 strains from different epidemiological background. Source: Robert Koch Institute and Prof. Dr. Christa Ewers

Recent Publications:

http://www.researchgate.net/profile/Torsten_Semmler

Date: 28.04.2016