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Mariia Zmyslia

Annette Brandel

Mycobacterial Membrane Transporter – An Entry Way for Therapeutic Intervention

Principal Investigator: Prof. Dr. Claudia Jessen-Trefzer 

Institute Of Organic Chemistry
Albertstr. 21, room 02.003
79104 Freiburg

Phone: +49 (0) 761 203 6039

mariia.zmyslia@ocbc.uni-freiburg.de

Abstract

To date, approximately one-third of the world’s population is harboring Mycobacterium tuberculosis (M. tuberculosis, Mtb), the causative pathogen of Tuberculosis (TB), a disease recognized by the World Health Organization as a world health threat.1 Two major hurdles in TB drug development are the impermeability of the mycobacterial cell wall to small molecules and the action of bacterial efflux pumps that actively transport drugs out of the cell.1 The acknowledged approach of engaging membrane transporters in directed drug uptake or as drug targets is very promising to overcome the thick and waxy cell membrane as a major hurdle in drug development. This strategy however will certainly require a more detailed understanding of the transporters and their dedicated substrates present in mycobacteria. We aim contribute to this field in characterizing membrane transporters in various mycobacterial species.

In this project, we want to determine uptake transporters for a subset of nutrient molecules and analyze their differential expression in relevant mycobacterial species (Mycobacterium smegmatis, Mycobacterium abscessus subsp. abscessus, Mycobacterium bovis BCG and Mycoabcterium tuberculosis H37Ra). Comparing these four species is especially interesting, as they comprise fast and slow-growing strains, which originate from different habitats; hence pose different demands in terms of required energy and carbon sources.

  • Methods
  • Microbiological methods as microbial identification, staining, engineering, survey, culturing and manipulation
  • Proteomics

 

Publications

Zmyslia M., Fröhlich K., Dao T., Schmidt A., Jessen-Trefzer C. Deep proteomic investigation of metabolic adaptation in mycobacteria under different growth conditions. Manuscript submitted for publication

Lohner P., Zmyslia M., et al. Inside a Shell – Organometallic catalysis inside encapsulin nanoreactors. Ang. Chem. Int. Ed. (2021)

Ebensperger P., Zmyslia M., Lohner P., Braunreuther J., Deuringer B., Becherer A., Süss R, Fischer A., Jessen-Trefzer C. A dual-metal catalyzed sequential cascade reaction in an engineered protein cage. ChemRxiv (2022)