Communication by bacteria as a therapeutic target for medicines.
FRANKFURT. Bacteria communicate by means of chemical signals and can develop common characteristics through this "agreement" and also develop their potential pathogenic effects in this way. Scientists working with Dr. Helge B. Bode, an Merck-endowed professor for molecular biotechnology at the Goethe University in Frankfurt, and Dr. Ralf Heermann from the department of microbiology at the Ludwig Maximilian University in Munich, have now described a hitherto unknown communication pathway that appears to be widely distributed. They report on this in the journal Proceedings of the National Academy of Science.
The investigation of bacterial communication is also of medical interest. This is because the bacterial communication pathways are a possible therapeutic target for new medicines. If the relevant communication options are prevented, the bacteria cannot develop their pathogenic properties. "When pathogens are no longer destroyed by antibiotics as we have seen to date, but rather be impaired beforehand the formation of the pathogenic properties, the danger of resistance development would be substantially reduced", says Bode.
Different types of bacteria also have different methods of communication. The team lead by Heerman and Bode had already discovered a new bacterial communication pathway in 2013. Now they have succeeded in decoding a further new and widely distributed chemical type of bacterial communication.
To date, the best known communication between bacteria occurs via the N-acyl homoserine lactone (AHL): The enzyme Luxl produces signals that are recognised by the LuxR receptor, at which point the bacteria develop certain properties and modulate their behaviour towards one another. Since a certain number of bacteria must be available for this to occur, this process is known as "quorum sensing".
However, Heermann's and Bode's working groups investigate bacteria that possess a LuxR receptor, but not the enzyme Luxl. In the current study, the microbiologists have investigated the bacteria Photorhabdus asymbiotica, which is a deadly pathogen in insects, which also infects humans and can cause skin infections. These bacteria communicate via the signal molecule dialkylresorcinol, which recognised the associated LuxR receptor. "The influence on the pathogenic properties of the bacteria is at its strongest in this 'quorum sensing' system. P. asymbiotica requires dialkylresorcinol and in this way coordinates the communication with the conspecifics for the successful infection of the larvae", says Helge Bode, whose group in 2013 also described the biosynthesis of this new signal molecule.
The researchers have not only investigated P. asymbiotica, but also a series of other bacterial genomes. The newly discovered signal pathway appears to be widely distributed. "We were able to identify several other bacteria that are pathogenic to humans that also do not express Luxl and also possess this ability for forming these signals", says Heerman.
Sophie Brameyer, Darko Kresovic, Helge B. Bode and Ralf Heermann:
Dialkylresorcinols as bacterial signaling molecules
In: PNAS 112 (2), 572-577.
Prof. Helge Bode, Merck endowed Professor for Molecular Biotechnology, Biosciences Department & Buchmann Institute for Molecular Life Sciences, Campus Riedberg, Tel.: (069) 798-29557, H.Bode@bio.uni-frankfurt.de.
Image can be downloaded at: www.uni-frankfurt.de/53683200
The insect larvae were infected with P. asymbiotica. Since the bacteria are bioluminescent, the larvae glow in the dark. The pathogenicity of organisms pathogenic to humans is frequently investigated in insect models. (Figure: Ralf Heermann, LMU).
Biochemists uncover an elementary energy metabolism process: They unlocked the structure of mitochondrial complex 1, a large protein complex in the respiratory chain , and at the same time learnt new aspects of its function.
Mitochondria produce ATP, the energy currency of the body. The driver for this process is an electrochemical membrane potential, which is created by a series of proton pumps. These complex, macromolecular machines are collectively known as the respiratory chain. The structure of the largest protein complex in the respiratory chain, that of mitochondrial complex I, has been elucidated by scientists from the Frankfurt "Macromolecular Complexes" cluster of excellence, working together with the University of Freiburg, by X-ray diffraction analysis.
"Mitochondrial complex I plays a critical role in the production of cellular energy and has also been associated with the onset of diseases, such as Parkinson's disease", explains Volker Zickermann, an assistant professor at the Institute for Biochemistry II at the Goethe University. In order for the respiratory chain to function, there must be consistently sufficient amounts of oxygen available in all the cells in our bodies. The energy released during biological oxidation is used to transport protons from one side of the inner mitochondrial membrane to the other. The resulting proton gradient is the actual "battery" for ATP synthesis.
What surprised the researchers: Previous studies suggested that redox reactions and proton transport in complex I occurred spatially isolated from one another. The Frankfurt scientists in Zickermann's working group and the working groups led by Prof. Harald Schwalbe and Prof. Ulrich Brandt have now been able to deduce how the two processes are connected to one another from the detailed analysis of the structure. They have therefore made an important contribution towards the understanding of an elementary process in energy metabolism.
It has long been known that complex I can switch reversibly between an active and inactive form. This has been interpreted as a protective mechanism against the formation of dangerous free oxygen radicals. The structure now clearly indicates how these two forms are differentiated from one another and transformed into one another. "The research results thus also give important information about the molecular basis of a pathophysiologically significant property of complex I that may be significant for the extent of tissue damage after a myocardial infarction," explains Zickermann.
Mechanistic insight from the crystal structure of mitochondrial complex I
V Zickermann et al.; Science, doi: 10.1126/science.1259859; 2015
The ABC4Trust project will present its results in the offices of the Hessian State Delegation to the European Union in Brussels
FRANKFURT/BRUSSELS One of the most widely recognized EU projects of Frankfurt's Goethe University will present its results on Tuesday (20/1) in the offices of the Hessian State Delegation to the European Union in Brussels: "ABC4Trust" is the acronym for an international project, for which Frankfurt Professor Kai Rannenberg is the spokesman. The project has developed solutions that will markedly increase the trustworthiness of personal data in the Internet while offering optimal privacy protection. In addition to the President of Goethe University, Prof. Dr. Birgitta Wolff, participants in the demonstration of the project results this coming Tuesday will also include Günther Oettinger or a representative of the Commissioner for Digital Economy and Society and Jan Albrecht, member of the European Parliament, Greens/EFA and rapporteur for the European General Data Protection Regulation.
The first three letters of ABC4Trust stand for "attribute-based credentials". The intention is to supply any Internet provider with only the relevant features (attributes) of the user in each case, but the attributes will also be furnished with a type of credibility certificate (credential) from an entity trusted by the provider. Here is an example: If someone buys a book over the Internet, the online merchant does not need to know anything about the purchaser's date of birth, blood group or hobbies shared with friends. Such information may be important in other Internet contexts, for example when contacting a health insurer or in a chat with friends. But what is of prime importance to the online merchant is that the user's account data is correct. The user can demonstrate this with a bankcard or credit card.
The user can store his "credentials" in a type of wallet, from which he can display the important attributes in each case. This is clearly better for the user than the current situation in the Internet, in which identity information is repeatedly queried from the source, the so-called "identity provider". Rannenberg, who has occupied the Deutsche Telekom Chair for "Mobile Business & Multilateral Security" since 2002, comments: "Since 2009, ABC4Trust has been developing a Privacy ABC-based system for electronic identification that allows users to shield their privacy and simultaneously offers security to their counterpart – the service provider. We have successfully tested the system in two pilot applications; a communications platform in a school in Sweden and an anonymous course evaluation system at the University of Patras."
A total of approximately 50 scientists have cooperated in various sub-projects, and the EU has supported ABC4Trust with just under 9 million Euros since 2010 from the 7th Research Framework Programme. In addition to Goethe University, the international project consortium includes Unabhängiges Landeszentrum für Datenschutz Schleswig-Holstein, Darmstadt Technical University and non-university research institutions from Denmark and Sweden, corporations such as IBM, Microsoft and Nokia Networks, and an encryption specialist from France.
A variety of pilot applications will be presented at the closing event in Brussels. The project also looks at ways in which the two advanced technologies for identity management using "attribute-based credentials" (both from American providers: U-Prove from Microsoft and Idemix from IBM) can be sensibly linked. The ABC4Trust project has been built using both of these technologies, so that the user is not dependent on one management system or the other, but can instead choose between them. ABC4Trust is also intended to be an openly accessible technology, which is a research condition required by the EU. The project team therefore had to bring together all the players. "That was not always particularly easy, but we managed to do it!", notes programme director Prof. Rannenberg.
At the presentation this coming Tuesday, he and his international colleagues will also offer a look forward at future developments in identity management. These include the use of these privacy ABCs in mobile devices such as smartphones and tablets, so that privacy can be better protected in those fields as well. The guests at this event in the Hessian State Delegation Office will also include: Michael Garcia (Deputy Director of the "National Strategy for Trusted Identities in Cyberspace" of the National Institute for Standardization and Technology (NIST) of the US Department of Commerce) and Achim Klabunde (Manager of the IT policy sector for the European Data Protection Supervisor).
Participation in the final event (20 January 9:30 am – 6:00 pm) is still open for interested parties and journalists; registration at: https://abc4trust.eu/index.php/events/177-summit-announce
Information Prof. Dr. Kai Rannenberg, Deutsche Telekom Endowed Professor of "Mobile Business & Multilateral Security", Department of Economics and Business Administration, Campus Westend, Tel. 069-79834701, Kai.Rannenberg@m-chair.de, firstname.lastname@example.org; https://www.datenschutzzentrum.de/projekte/abc4trust/, English-language project website at https://abc4trust.eu/summit