2021 Swiss TB Award

The SwissTB award has been given this year to the three first authors of a Nature paper. The awardees are Fabian Arnold, Miriam Sarah Weber and Imre Gonda from the University of Zurich.

In this work published in the scientific journal Nature the three authors investigated the role of the ABC transporter IrtAB in the siderophore metabolism of Mycobacterium tuberculosis (Mtb). Siderophores are small organic molecules produced by Bacteria that bind iron with very high affinity. Mtb produces two different siderophores: mycobactin (MBT), a membrane-anchored siderophore, and carboxymycobactin (cMBT) a soluble and secreted siderophore. During infection, iron is not freely available to Mtb but trapped by host proteins in order to prevent Mtb access from this essential element for growth. Thus, the siderophores MBT and cMBT are crucial elements of survival and virulence of Mtb. The transporter IrtAB from Mtb belongs to the family of ABC transporters, and transports substrates across the bacterial membrane by using ATP hydrolysis as energy source. IrtAB was postulated to be involved in siderophore uptake in Mtb, but the evidence in the literature was scarce and limited to a few in vivo studies. In this work, the authors could show by in vivo and in vitro experiments, that IrtAB is the main transporter for siderophores and that it played an essential role especially in the import of MBT. By combining the structural techniques of X-ray crystallography and Cryo-EM, the authors could solve the molecular structure of IrtAB at atomic resolution. These results will lead the way to understand the exact transport mechanism and allow for the design of targeted drugs against the siderophore transport of Mtb.

PDF presentation