Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Insect Antibiotic Provides New Way to Eliminate Bacteria

15.11.2018

An antibiotic called thanatin attacks the way the outer membrane of Gram-negative bacteria is built. Researchers at the University of Zurich have now found out that this happens through a previously unknown mechanism. Thanatin, produced naturally by the spined soldier bug, can therefore be used to develop new classes of antibiotics.

The global emergence of multi-drug resistant bacteria is posing a growing threat to human health and medicine. “Despite huge efforts from academic researchers and pharmaceutical companies, it has proven very difficult to identify effective new bacterial targets for antibiotic discovery,” says John A. Robinson from the Department of Chemistry at UZH.


“One of the major challenges is identifying new mechanisms of antibiotic action against dangerous Gram-negative bacteria.” This group of bacteria includes a number of dangerous pathogens, such as Pseudomonas aeruginosa, which causes life-threatening lung infections, and pathogenic Escherichia coli strains.

Elimination of outer protective shield

An interdisciplinary team of chemists and biologists from UZH and ETH Zurich have now uncovered how thanatin – an antibiotic produced naturally by the spined soldier bug Podisus maculiventris – targets Gram-negative bacteria. The insect’s antibiotic prevents the outer membrane of the bacteria from forming – an unprecedented mechanism in an antibiotic.

All Gram-negative bacteria have a double cell membrane, with the outer membrane taking on an important defensive function and helping the bacteria to block the entry of potentially toxic molecules into the cell. The outside of this membrane is made up of a protective layer of complex fat-like substances called lipopolysaccharides (LPS), without which the bacteria could not survive.

Focusing on protein-protein interactions

Using state-of-the-art methods, the Zurich researchers succeeded in proving that thanatin disrupts the transport of LPS molecules to the outer membrane. The transport pathway consists of a super-structure of seven different proteins that assemble to form a bridge from the inner membrane across the periplasmic space to the outer membrane.

LPS molecules cross this bridge to the cell’s surface, where they form part of the structure of the outer membrane. Thanatin is able to block the protein-protein interactions that are needed to form the bridge. As a result, LPS molecules are prevented from reaching their destination and the biogenesis of the entire outer membrane is inhibited – which is fatal for the bacteria.

New potential clinical candidates

“This is an unprecedented mechanism of action for an antibiotic and immediately suggests ways to develop new molecules as antibiotics targeting dangerous pathogens,” explains Robinson. “This finding shows us a way to develop substances that specifically inhibit protein-protein interactions in bacterial cells.”

This new mechanism is already being used by an industry partner – Polyphor AG in Allschwil near Basel – to develop new potential clinical candidates. The company has a proven track record of success in this area and has recently also developed the antibiotic murepavadin in cooperation with UZH.

Murepavadin is currently in phase III clinical tests in patients with life-threatening lung infections caused by Pseudomonas aeruginosa. “Another new antibiotic targeting other Gram-negative pathogens would be a very welcome addition to the new medicines urgently needed for effective antibacterial therapy,” says Robinson.

Wissenschaftliche Ansprechpartner:

Prof. John A. Robinson
Department of Chemistry
University of Zurich
Phone: +41 79 438 23 33
E-mail: john.robinson@chem.uzh.ch

Originalpublikation:

Stefan U. Vetterli, Katja Zerbe, Maik Müller, Matthias Urfer, Milon Mondal, Shuang-Yan Wang, Kerstin Moehle, Oliver Zerbe, Alessandra Vitale, Gabriella Pessi, Leo Eberl, Bernd Wollscheid, and John A. Robinson. Science Advances, 2018, 16 November. DOI: 10.1126/sciadv.aau2634

Beat Müller | Universität Zürich
Further information:
http://www.uzh.ch/

More articles from Life Sciences:

nachricht Too much of a good thing: overactive immune cells trigger inflammation
16.09.2019 | Universität Basel

nachricht The sleep neuron in threadworms is also a stop neuron
16.09.2019 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tomorrow´s coolants of choice

Scientists assess the potential of magnetic-cooling materials

Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....

Im Focus: The working of a molecular string phone

Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.

This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.

Im Focus: Milestones on the Way to the Nuclear Clock

Two research teams have succeeded simultaneously in measuring the long-sought Thorium nuclear transition, which enables extremely precise nuclear clocks. TU Wien (Vienna) is part of both teams.

If you want to build the most accurate clock in the world, you need something that "ticks" very fast and extremely precise. In an atomic clock, electrons are...

Im Focus: Graphene sets the stage for the next generation of THz astronomy detectors

Researchers from Chalmers University of Technology have demonstrated a detector made from graphene that could revolutionize the sensors used in next-generation space telescopes. The findings were recently published in the scientific journal Nature Astronomy.

Beyond superconductors, there are few materials that can fulfill the requirements needed for making ultra-sensitive and fast terahertz (THz) detectors for...

Im Focus: Physicists from Stuttgart prove the existence of a supersolid state of matte

A supersolid is a state of matter that can be described in simplified terms as being solid and liquid at the same time. In recent years, extensive efforts have been devoted to the detection of this exotic quantum matter. A research team led by Tilman Pfau and Tim Langen at the 5th Institute of Physics of the University of Stuttgart has succeeded in proving experimentally that the long-sought supersolid state of matter exists. The researchers report their results in Nature magazine.

In our everyday lives, we are familiar with matter existing in three different states: solid, liquid, or gas. However, if matter is cooled down to extremely...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Society 5.0: putting humans at the heart of digitalisation

10.09.2019 | Event News

Interspeech 2019 conference: Alexa and Siri in Graz

04.09.2019 | Event News

AI for Laser Technology Conference: optimizing the use of lasers with artificial intelligence

29.08.2019 | Event News

 
Latest News

Too much of a good thing: overactive immune cells trigger inflammation

16.09.2019 | Life Sciences

Scientists create a nanomaterial that is both twisted and untwisted at the same time

16.09.2019 | Materials Sciences

Researchers have identified areas of the retina that change in mild Alzheimer's disease

16.09.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>