Biogenic Insecticides Described
Freiburg, 01.03.2010
In the latest issue of the renowned scientific journal Science (vol. 327, pp. 1139–1142), researchers from the University of Freiburg report on their discovery of a new mode of action of insecticidal toxins from Photorhabdus luminescens, a bacterium which lives in a symbiotic relationship with nematodes. The tiny worms enter insect larvae through natural openings, where they proceed to „cough up“ the bacteria, so to speak. Bacterial toxins produced by the light-emitting bacteria kill the insect larvae (see photo), thus creating a larger reservoir of nourishment for the proliferation of nematodes and bacteria. For this reason, the worms and their bacteria are often used as biogenic insecticides.
Photorhabdus luminescens produces
various toxins which form large toxin complexes (Tc proteins). The biologically
active complex consists of the three components TcA, TcB, and TcC. Until now,
scientists have not succeeded in describing the enzymatic activity or the mode
of action of these toxins.
A team of researchers at the University of Freiburg led by Prof. Dr. Dr. Klaus Aktories and Prof. Dr. Gudula Schmidt investigated the effects
of the toxins on insect and mammal cells together with researchers from the
company Dow AgroSciences (USA) and Prof. Dr. Hans
Georg Mannherz (University of Bochum and Max Planck
Institute for Molecular Physiology in Dortmund). They were able to
demonstrate that the biological activity is localized in the TcC components TccC3 and TccC5. The two toxin
components are enzymes which inhibit essential defense mechanisms of immune
cells, such as the intake and elimination of bacteria. The toxins act on the
target cells of the insect larvae in two different ways: TccC3 modifies the
cytoskeleton protein actin directly at the amino acid threonine-148 by adding
ADP-ribose. This leads to the elimination of a regulator of actin (thymosin-β4),
resulting in a greatly increased polymerization of the cytoskeleton. The second
toxin, TccC5, effects changes in Rho proteins, the switching proteins
for the regulation of the actin cytoskeleton. These regulators are switched on
and off again in the cell. TccC5 modifies the switch at the amino acid glutamine-63,
also by adding ADP-ribose, and prevents it from being switched off. The
permanently active Rho protein then promotes the
polymerization of actin. Together, the two toxins lead to a strong aggregation
and cluster building in the actin cytoskeleton which is incompatible with
normal cellular function and immune defense. In order to enter the insect
cells, the toxins TccC3 and TccC5 need TcA as it builds the pores in the host
cells they likely use to penetrate into the inside of the cell.
Tc proteins have also been identified in human pathogenic bacteria such as Yersinia
pseudotuberculosis and Yersinia
pestis. A full explanation of the
molecular mechanisms of the prototypical tc proteins is thus of paramount
importance for reaching an understanding of other tc proteins from insecticides
and human pathogenic bacteria.
The original title of the publication by Alexander
E. Lang, Gudula Schmidt, Andreas Schlosser, Timothy D. Hey, Ignacio M.
Larrinua, Joel J. Sheets, Hans G. Mannherz, and Klaus Aktories in Science is „Photorhabdus
luminescens Toxins ADP-Ribosylate Actin and RhoA to Force Actin
Clustering.“
Captions: Galleria mellonella (greater wax moth) infected with Photorhabdus luminescens. (A) Larvae of the greater wax moth after infection with P. luminescens, left, not infected; middle, after 24 hours; right, after 48 hours. (B) Bioluminescence of P. luminescens. After infecting the insect larvae, P. luminescens begins to glow. (C–F) Effect of P. luminescens toxins on isolated primary blood cells (hemocytes) of Galleria mellonella. Control cells (C), treated with TccC3 (D), TccC5 (E), and TccC3 + TccC5 (F). The two toxins destroy the cytoskeleton of target cells.
Photos: © Alexander E. Lang
Contact:
Prof. Dr. Dr. Klaus Aktories
Albert-Ludwig University of Freiburg
Institute of Experimental and Clinical Pharmacology and Toxicology
Phone: ++49-761-203-5301
Homepage: www.pharmakologie.uni-freiburg.de
Email: klaus.aktories@pharmakol.uni-freiburg.de