Lead


Lay summary

) strains that inhibits the proteasome in host cells by a novel mechanism. Pss(syringae  pv. Pseudomonas syringae Bacterial plant pathogens are able to manipulate physiology and defense mechanisms of their hosts by means of so-called effectors, which often are proteins encoded by the pathogen that are injected into the host cells by a special transport system, the type III secretion system. In addition to type III effector proteins, phytopathogenic bacteria are known to synthesize a variety of small molecules acting as toxins or virulence factors. In previous projects, we have identified such a virulence factor, named syringolin A. Syringolin A is a small peptide derivative secreted by certain

The experiments proposed in this research project aim at the further elucidation of the biology of syringolin A and similar compounds (collectively dubbed syrbactins). To reach its target, syringolin A must enter plant cells. We will try to elucidate how syringolin A is taken up by plant cells and to identify the uptake transport system that is postulated to exist. These experiments will involve functional expression of candidate Arabidopsis peptide/oligopeptide transporter cDNAs, or if necessary, an Arabidopsis cDNA library, in yeast. Other experiments will aim at the identification of the exact mechanisms of how proteasome inhibition benefits the pathogen.

is postulated to produce. The proposed research has the potential to enlarge the syrbactin class of proteasome inhibitors and to predict occurrence, structure and function of syrbactins from genome and metagenome sequence data with high confidence. Because proteasome inhibitors are a promising class of anti-cancer agents, the results of the proposed research may also have medical implication.Photorhabdus luminescens . In the current project, we will  isolate and structurally and biochemically characterize the putative syringolin A analogon which the insect pathogen Photorhabdus asymbioticaand Burkholderia oklahomensis , an insect pathogen, as well as the human pathogens Photorhabdus luminescensa dangerous human pathogen and causal agent of melioidosis, Burkholderia pseudomallei, . We previously have isolated and characterized the gene clusters encoding the syringolin A and glidobactin A synthetases which turned out to exhibit a characteristic gene architecture. Similar gene clusters were found in five taxa among the more than 1500 completely sequenced bacterial genomes, including BurkholderialesSyringolin A defines a novel class of proteasome inhibitors, dubbed syrbactins, that includes glidobactin A, an antifugal and anti-tumor agent produced by a bacterium belonging to the