Linear ubiquitination controls Salmonella growth
May 2017. A team around Ivan Dikic and Mike Heilemann (Chemistry Department, Goethe University) gained unprecedented insight into the mechanism by which cells fight Salmonella infections. Upon intracellular invasion, bacteria are usually rapidly surrounded by a coat of ubiquitin, the function of which remained unclear until now. Combining super-resolution microscopy with cell biological analysis, the researchers now discovered that distinct ubiquitin chains transform the bacterial surface into a molecular signalling platform. They were able to visualize the nanoscale distribution of different ubiquitin chains on the bacterial surface. One chain type, so called linear chains, specifically triggers pro-inflammatory signalling cascades, thereby restricting bacterial proliferation. In addition, the researchers identified the deubiquitinase OTULIN as a regulator capable of limiting this reaction – a very important notion considering the fact that excessive inflammation is one of the major causes of tissue damage following bacterial infection.
In collaboration with colleagues from Japan, the Frankfurt researchers now published their results in the latest online issue of Nature Microbiology. Their work is an excellent example for interdisciplinary collaboration and was enabled by funding of several large research networks, e.g. the Cluster of Excellence Macromolecular Complexes, the CRC 1177 on selective autophagy and the LOEWE ubiquitin network. The discovery paves the way for many new projects. Very recently, Ivan Dikic obtained one of the prestigious ERC Advanced Grants in which he will investigate the role of ubiquitin in modulating the host-pathogen interaction in more detail.
Salmonellen-Bakterien in einer menschlichen Zelle, umgeben von einem Mantel aus verschiedenartigen Ubiquitin-Markierungen. Lila repräsentiert linear-verknüpfte Ubiquitin-Ketten, grün alle Ubiquitin-Markierungen. Aufgenommen mittel hochauflösender Mikroskopie (dSTORM). Copyright : Mike Heilemann/Ivan Dikic
Ein Salmonellen-Bakterium in einer menschlichen Zelle, umgeben von einem Mantel aus verschiedenartige Ubiquitin-Ketten. Lila repräsentiert linear-verknüpfte Ubiquitin-Ketten, grün alle Ubiquitin-Markierungen. Aufgenommen mittel hochauflösender Mikroskopie (dSTORM). Copyright : Mike Heilemann/Ivan Dikic
Ein Salmonellen-Bakterium in einer menschlichen Zelle, umgeben von einem Mantel aus Ubiquitin. Die farbigen Punkte stellen einzelne linear verknüpfte Ubiquitin-Ketten dar. (Blaue Punkte sind näher am Betrachter, die gelb-rötlichen weiter entfernt.) Aufgenommen mittels hochauflösender Mikroskopie (3D-dSTORM). Copyright : Mike Heilemann/Ivan Dikic
Contact:
Prof. Dr. Ivan Dikic
Institute for Biochemistry II & Buchmann Institute for Molecular Life Sciences
Goethe University Frankfurt, Germany
dikic(at)biochem2.uni-frankfurt.de
Prof. Dr. Mike Heilemann
Institute of Physical and Theoretical Chemistry
Goethe University Frankfurt, Germany
heilemann(at)chemie.uni-frankfurt.de