Metabolic Responses to Bacterial Pathogens

Tine Kliim Nydahl

Research focus 
Infectious diseases are among the leading causes of death worldwide and the number of outbreaks and disease richness is increasing globally. In addition, antimicrobial agents are losing their ability to fight infections because microorganisms are becoming increasingly resistant to existing antimicrobials. The global threat posed by antimicrobial resistance is compounded by recent lack of successful strategies for developing novel antimicrobials. However, a recent report suggests that central metabolic pathways of bacterial pathogens potentially could serve as an alternate drug target space for the next generation of antibiotics.

Success in targeting bacterial central metabolism relies on an elucidation of metabolic host responses to bacterial infections. The metabolic interplay between pathogen and host cell remains poorly understood, in part owing to methodical limitations. A new method, dissolution Dynamic Nuclear Polarization (dDNP) can provide >10.000 fold enhancements in spectral signal-to-noise ratio of NMR spectroscopy experiment. This significant improvement of sensitivity allows for monitoring of biochemical reactions directly in living systems. 

dDNP-NMR has the potential to provide detailed information on the metabolic host response to bacterial infections as well as the effect of drugs as well as probiotics/prebiotics on the interlinked metabolism between pathogen and host cell. Development of sensitive assays based on dDNP-NMR and infection models could thus lay the foundation for a platform for evaluation of new antimicrobial therapies targeting bacterial central metabolism – which is the motivation for this project. The research is divided into two parts: the establishment of a non-invasive method for studying metabolic interactions between intracellular bacterial pathogens and their hosts in real-time and the validation of this method. 

Scientific output 
Find Tine's publications at DTU's online research database ORBIT

Funding 
The project is funded by Danish National Research Foundation as part of the HYPERMAG Center of Excellence (DNRF124). 

Supervisors 
Associate Professor Pernille Rose Jensen and Senior Research Mathilde H. Lerche.

Project period 
January 2018 - February 2022 (maternity leave June 2018 - July 2019)

 

 

 

Contact

Tine Kliim Nydahl
PhD student
DTU Health Tech
http://www.hypermag.dtu.dk/Research/PhD-projects/Tine-Kliim-Nydahl
29 JANUARY 2020