Infective entomopathogenic nematodes are minute worms that penetrate insect larva and serve as transport vehicles for the bacterium Photorhabdus luminescens, which lives in their alimentary tract.
After larva penetration the nematodes release these bacteria, which secrete toxins that compromise the immune system of the larvae. Thus the nematodes are used together with the bacterium as insecticide. The exact mechanism of action of the Photorhabdus luminescens had been unknown to date.
Together with colleagues from Freiburg, Prof. em. Hans Georg Mannherz (Medical Faculty of the RUB and the Max-Planck-Institute for Molecular Physiology, Dortmund) has now managed to elucidate this process. Specific subunits of the bacterial toxin complex that inhibit essential defence reactions of immune cells are of instrumental significance. Some of the bacterial infectious toxins bear resemblances to toxins of human pathogenic bacteria, e.g. the bacteria that cause pulmonary and bubonic plaque may make use of similar mechanisms. The researchers have published their findings in the current volume of SCIENCE.
Worms transport the bacteria to the target
Photorhabdus luminescens lives in symbiosis with nematodes. The minute worms penetrate insect larvae via natural openings and then more or less "regurgitate" the bacteria. Bacterial toxins produced by this light-emitting bacterium kill the insect larvae thus creating a large food reservoir for the proliferation of nematodes and bacteria.
Two subunits of the toxin complex are biologically active
Photorhabdus luminescens produces diverse toxins that generate large toxin complexes (Tc proteins). The biologically active complex consists of the three components TcA, TcB and TcC. So far the mechanism of action of these toxins has been unknown. Together with the Dow AgroSciences (USA) and Prof. em. Mannherz and research scientists in Freiburg, working under the auspices of Prof. Klaus Aktories and Prof. Gudula Schmidt, investigated the impact of the toxins on insect and mammalian cells. They were able to demonstrate that the biological activity is located in the TcC components TccC3 and TccC5. The two toxin components are enzymes that inhibit the essential defence reactions of immune cells, e.g. the phagocytosis of bacteria.
Toxins function in two ways
The toxins act on the target cells of the insect larvae in two different ways. TccC3 modifies the cytoskeletal protein actin (ADP-ribosylation) to such an extent that it is no longer controlled by the regulator protein thymosin beta 4. This results in a significant polymerisation of the actin. The second toxin, TccC5, changes so-called Rho proteins, i.e. the switch proteins responsible for the regulation of the actin cytoskeleton. Normally these regulators are switched on and off within the cell. TccC5 modifies the switch by blocking the switching-off procedure. Subsequently the permanently active Rho protein enhances the polymerisation of actin. Together the two toxins lead to a strong aggregation and even clustering of the actin cytoskeleton, which is incompatible with the normal cellular function or immune defence reaction. TcA, which forms pores in host cells, is necessary to enable the toxins TccC3 and TccC5 to enter the insect cells. The toxins probably infiltrate the interior of the cells through these pores.
Decisive knowledge for the comprehension of Tc proteins
Tc Proteins have also been identified in human pathogenic bacteria such as Yersinia pseudotuberculosis and Yersinia pestis. As Prof. Mannherz pointed out, the clarification of the molecular mechanism of prototypical Tc proteins is thus of fundamental importance for the comprehension of other Tc proteins from insecticidal and human pathogenic bacteria.
Alexander E. Lang, Gudula Schmidt, Andreas Schlosser, Timothy D. Hey, Ignacio M. Larrinua, Joel J. Sheets, Hans G. Mannherz and Klaus Aktories: "Photorhabdus luminescens Toxins ADP-Ribosylate Actin and RhoA to Force Actin Clustering." In: Science 26 February 2010 327: 1139-1142 [DOI: 10.1126/science.1184557]
Further InformationProf. em. Hans Georg Mannherz, Abteilung für Anatomie und Embryologie der Ruhr-Universität Bochum und Abteilung für Physikalische Biochemie des Max-Planck-Instituts für Molekulare Physiologie, Dortmund, Germany
Editor: Meike Drießen
Dr. Josef König | idw
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences