Researchers at the University of Würzburg and the Spanish Cancer Research Centre have gained new insights into the pathogen that causes tuberculosis. The work published in Nature provides the basis for a new approach in antibiotic therapy.
Tuberculosis is a highly contagious infectious disease that is typically spread through aerosols and mainly affects the lungs. According to the World Health Organization (WHO), an estimated 1.7 million people die from such an infection worldwide every year. In addition, a quarter of the world's population carries a form of tuberculosis that lies dormant without symptoms for a long time, but can break out eventually.
Nanomachines in the cell envelope
During infection Mycobacterium tuberculosis, the main causative agent of tuberculosis, secretes a large number of effector proteins through type VII secretion systems – small nanomachines which are composed of proteins that reside in the cell envelope. The effector proteins are specialized in fighting the immune defense or enable the uptake of nutrients to ensure the bacterial survival in the host. How these central secretion systems work, is still poorly understood.
Scientists from the Julius-Maximilians-Universität Würzburg (JMU) and the Spanish Cancer Research Centre CNIO (Centro Nacional de Investigaciones Oncológicas) have now succeeded in deciphering the molecular architecture of these nanomachines. Dr. Sebastian Geibel, who heads a research group at the Institute of Molecular Infection Biology funded by the Bavarian Elite Network and who is also affiliated with the Rudolf Virchow Centre of the JMU, was in charge of this work. The scientists have published their work in the current issue of the journal Nature.
Measurements at very low temperatures
Over the past five years, the research group of Dr. Geibel has worked intensively on the stable reconstitution of one of these secretion machines and the preparation of the sensitive sample for measurements on the cryo electron microscope, which requires the protein complexes to be shock frozen under defined conditions.
In collaboration with the research group of Oscar Llorca in Madrid, which computed three-dimensional maps of the protein complex using a sophisticated data processing strategy, the researchers from Würzburg were able to create a model of its molecular structure. The researchers were able to identify important elements of the nanomachine that form the transport pore as well as to locate elements that convert chemical energy into motion and thus drive the transport of effector proteins through the pore.
New approach for new drugs
The findings of the researchers lead to a deeper functional understanding of Type VII secretion systems. In times of rising resistance of mycobacteria to the antibiotics in use and no effective vaccination against tuberculosis in place, the researcher provide an important basis for the development of novel antibiotics that target the assembly or function of the type VII secretion systems.
Dr. Sebastian Geibel, T: +49 931 31-84590, firstname.lastname@example.org
Architecture of the mycobacterial type VII secretion system. Nikolaos Famelis, Angel Rivera-Calzada, Gianluca Degliesposti, Maria Wingender, Nicole Mietrach, J. Mark Skehel, Rafael Fernandez-Leiro, Bettina Böttcher, Andreas Schlosser, Oscar Llorca & Sebastian Geibel. Nature, 9. October 2019, DOI 10.1038/s41586-019-1633-1.
Gunnar Bartsch | idw - Informationsdienst Wissenschaft
When predictions of theoretical chemists become reality
22.05.2020 | Technische Universität Dresden
From artificial meat to fine-tuning photosynthesis: Food System Innovation – and how to get there
20.05.2020 | Potsdam-Institut für Klimafolgenforschung
Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.
When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...
Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.
Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...
Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.
A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...
By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.
Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type...
Study co-led by Berkeley Lab reveals how wavelike plasmons could power up a new class of sensing and photochemical technologies at the nanoscale
Wavelike, collective oscillations of electrons known as "plasmons" are very important for determining the optical and electronic properties of metals.
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
25.05.2020 | Medical Engineering
25.05.2020 | Information Technology
25.05.2020 | Information Technology