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
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News