Function of ATP binding cassette (ABC) transporters in Mycobacterium tuberculosis with focus on carbohydrate permeases and antibiotic exporters

• Applicant: Professor Dr. Rainer Kalscheuer
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 193442298

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is the most severe killer among bacterial pathogens, causing about two million fatalities annually. Mtb is an obligate pathogen highly adapted to the intracellular conditions in the host. The Mtb genome encompasses 37 adenosine triphosphate (ATP)-binding cassette transporters (ABCtransporters). ABC transporters are transmembrane permeases that couple energy-releasing ATP hydrolysis to the translocation (import or export) of a substrate across a cell membrane, implicating that they might play important roles in interactions with the host cells. However, the function and substrate-specificity of most of these ABC-transporters and their role for virulence is unknown. Therefore, the planned studies aim at a functional characterization of Mtb ABCtransporters, focussing on putative sugar transporters and antibiotic exporters, principally by generating targeted gene deletion mutants in virulent Mtb. Phenotypic characterization of these mutants by physiological, chemical and biochemical analyses allows insight into the nature of the specific transporter substrates. Cell biological characterization of these mutants in infected macrophages and their subsequent evaluation in a mouse infection model will unveil a potential role of the ABC transporters for pathogenesis of Mtb. It is expected that these studies result in a deeper understanding of the physiological and metabolic adaptations of Mtb to the intracellular host environment potentially leading to novel antitubercular chemotherapeutic strategies.

• DFG Programme: Research Grants
• Major Instrumentation: HPLC System
• Instrumentation Group: 1350 Flüssigkeits-Chromatographen (außer Aminosäureanalysatoren 317), Ionenaustauscher