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Blocking the Iron Transport Could Stop Tuberculosis [innovations-report.com]:

"The transport protein, which is located in the bacterial membrane, is essential for the survival of the pathogens. If IrtAB is absent or not functioning, M. tuberculosis can no longer reproduce inside the human cell", says Seeger.

Iron transport protein works in the opposite direction

Using a combination of cryo-electron microscopy and X-ray crystallography, the researchers solved for the first time a high-resolution structure of the transport protein IrtAB. This analysis was done in collaboration with Ohad Medalia, professor at the Department of Biochemistry of UZH.

According to its spatial structure, IrtAB belongs to the so-called ABC exporters, which are typically involved in the efflux of molecules out of the bacterial cell. "However, we were able to show that IrtAB in fact imports mycobactins into M. tuberculosis. It therefore transports molecules in the opposite direction than expected," says Markus Seeger.

Together with scientists from the University of Texas, USA, the research team identified an additional peculiarity of the transport protein IrtAB: It can modify the iron bound to mycobactin after it is imported into the bacteria. The iron is thus released inside the cell and the empty mycobactin can be recycled.

Inhibiting the iron transport could lead to new tuberculosis drugs

"IrtAB is a potential drug target, because its deletion renders M. tuberculosis inactive and incapable of infection. With our structural and functional elucidation of IrtAB, we opened avenues to develop novel tuberculosis drugs that inhibit the iron transport into the bacteria", Seeger concludes. "In view of Covid-19, a disease that also affects the lungs, tuberculosis will likely play a more important role again in the future. It is quite conceivable that patients weakened by Covid-19 will show increased infection rates with tuberculosis," he adds.

Funding
  This research project was largely funded by the ERC Consolidator Grant 2017 of the European Research Council for the project "Discovery and molecular investigation of mycobacterial transporters responsible for iron acquisition" (MycoRailway) led by Markus Seeger.

Wissenschaftliche Ansprechpartner:

Prof. Dr. Markus A. Seeger
  Institute of Medical Microbiology
  University of Zurich
  Phone: +41 44 634 53 96
  E-mail: m.seeger@imm.uzh.ch

Originalpublikation:

Fabian M. Arnold, Miriam S. Weber, Imre Gonda et. al. The ABC exporter IrtAB imports and reduces mycobacterial siderophores. Nature. 25 March 2020. DOI: 10.1038/s41586-020-2136-9

Weitere Informationen:

https://www.media.uzh.ch/en/Press-Releases/2020/Tuberculosis.html [media.uzh.ch]

Kurt Bodenmüller | Universität Zürich

Further reports about: Covid-19 [innovations-report.com] Iron [innovations-report.com] TuBerculosis [innovations-report.com] X-ray crystallography [innovations-report.com] cryo-electron microscopy [innovations-report.com] lungs [innovations-report.com] mycobacterial [innovations-report.com] pathogens [innovations-report.com] transport protein [innovations-report.com] tuberculosis drugs [innovations-report.com]

Original Submission