We currently are funded by the European Research Council (ERC), Horizon 2020, and by the Lower Austria Education and Science Fund (NFB). Below you can read about our currently funded projects.
ERC Consolidator Grant 2014
Selective barriers to horizontal gene transfer (EVOLHGT)
Horizontal gene transfer (HGT) is a form of genic inheritance that occurs between individuals in a population or between species rather than from parent to offspring. HGT is most prevalent in bacteria, where it is an important source of novel metabolic pathways, pathogenicity factors, and antibiotic resistance.
In spite of the importance of HGT, we understand little about the evolutionary barriers to HGT. This proposal will outline a systematic experimental approach to elucidate factors that select for or against horizontally transferred genes, by pursuing three objectives. The first is to quantify intrinsic selection acting on newly transferred genes, by experimentally transferring and expressing several hundred genes across species boundaries. We will be able to systematically classify genes as resistant or permissive to transfer, examine the effect of the function and position in metabolic and regulatory networks on resistance to transfer, as well as identify any genes with substantial intrinsic benefits. The second objective is to examine the effect of evolutionary divergence on HGT, by determining whether genes from closely related species are more permissive to transfer than those from more divergent species. The final objective is to determine the role of the environment in shaping these selective effects. Understanding how robust the selective effects are to different environmental conditions will aid in evaluating the relative roles of genetics and the environment as factors in the evolutionary outcomes of HGT. Overall, this work will provide a systematic analysis of the roles of different factors in affecting the outcomes of horizontal gene transfer. Understanding this process in a quantitative fashion is critical to understanding bacterial adaptation and diversity.
Grant acronym: EVOLHGT
Grant number: 648440
Grant amount: € 1,820,865
Role: Single PI
NFB Life Science Call 2014
Relevance of phage transduction in transfer and persistence of antibiotic resistance in the medical environment
Hospital-acquired-infections caused by antibiotic resistant pathogens is a global concern to public health. Even the Obama Administration has recently acknowledged the need for innovative research to slow down the public health threat of antibiotic resistant bacteria with a National Strategy for Combating Antibiotic Resistant Bacteria (CARB). The increasing prevalence of antibiotic resistant and multi-drug-resistant pathogens has been shown to considerably expand the burden of disease, despite numerous infection control measures and modern hospital epidemiology. Thus, antimicrobial resistance in microbes is considered to be one of the major threats in medicine and public health worldwide. The horizontal spread of antimicrobial resistance between bacteria is a critical step in the development of resistance during therapy, the dissemination of resistance between different bacterial species, the acquisition of resistance from environmental sources, and the evolution of the bacterial host. An understanding of the mechanisms of horizontal transfer of antimicrobial resistance genes between microorganisms inside and outside of the host is essential to finding strategies to combat their spread. Current knowledge is that the transfer of resistance factors is largely due to conjugative plasmids or transposons and only to a minor extent transduction via bacteriophages. However, based on whole genome sequencing it has been hypothesized that the latter mechanism might play a substantially more important role in the transfer of antimicrobial resistance than is currently accepted. Recently we were able to show that phage transduction is of primary importance in the acquisition of therapeutically important resistance genes in Escherichia coli found on food. We reported that chicken meat carries a number of coli-phages capable of transferring antimicrobial resistance. High numbers of randomly tested phages were able to transduce one or more antimicrobial resistances. Phage transduction of specific resistance elements appears to be widely distributed. This mechanism of transfer may explain unanswered questions regarding the emergence and spread of antimicrobial resistant pathogens. In this proposal we hypothesize that transduction of antibiotic resistance by phages in the medical environment takes place and has important consequences for human health. Thus, the development of new control strategies to cope with phage persistence and transduction need to be found. Thus, we propose to investigate the significance of transduction in the medical environment for hospital-associated pathogens causing major problems by means of antibiotic resistance like Escherichia coli and Staphylococcus aureus. We will isolate and characterize antimicrobial resistance transferring phages, clarify the mechanisms of transfer, analyse the therapeutic importance and finally explore the transduced bacterial host for phage transmission and virulence.
Grant number: LSC14-006
Grant amount: € 307,610