Photorhabdus luminescens Toxins ADP-Ribosylate Actin and RhoA to Force Actin Clustering

Alexander E. Lang,^1,2,* Gudula Schmidt,^1,* Andreas Schlosser,³ Timothy D. Hey,⁴ Ignacio M. Larrinua,⁴ Joel J. Sheets,⁴ Hans G. Mannherz,^5,6 Klaus Aktories^1,

Abstract: The bacterium Photorhabdus luminescens is mutualistically associated with entomopathogenetic nematodes. These nematodes invade insect larvae and release the bacteria from their intestine, which kills the insects through the action of toxin complexes. We elucidated the mode of action of two of these insecticidal toxins from P. luminescens. We identified the biologically active components TccC3 and TccC5 as adenosine diphosphate (ADP)–ribosyltransferases, which modify unusual amino acids. TccC3 ADP-ribosylated threonine-148 of actin, resulting in actin polymerization. TccC5 ADP-ribosylated Rho guanosine triphosphatase proteins at glutamine-61 and glutamine-63, inducing their activation. The concerted action of both toxins inhibited phagocytosis of target insect cells and induced extensive intracellular polymerization and clustering of actin. Several human pathogenic bacteria produce related toxins.

¹ Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.
² Fakultät für Biologie, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.
³ Zentrum für Biosystemanalyse, Core Facility Proteomics, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.
⁴ Discovery Research, Dow AgroSciences, Indianapolis, IN 46268, USA.
⁵ Physikalische Biochemie, Max-Planck-Institut für molekulare Physiologie, 44227 Dortmund, Germany.
⁶ Abteilung für Anatomie und Embryologie, Ruhr-Universität Bochum, 44801 Bochum, Germany.

To whom correspondence should be addressed. E-mail: klaus.aktories{at}pharmakol.uni-freiburg.de

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