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The peptide derivative syringolin A, a product of a mixed nonribosomal peptide and polyketide synthetase, is secreted by certain strains of the phytopathogenic bacterium Pseudomonas syringae pv. syringae. Syringolin A was shown to be a virulence factor for P. syringae pv. syringae B728a because disease symptoms on its host Phaseolus vulgaris (bean) were greatly reduced upon inoculation with syringolin A-negative mutants. Syringolin A's mode of action was recently shown to be irreversible proteasome inhibition. Here, we report that syringolin A-producing bacteria are able to open stomata and, thus, counteract stomatal innate immunity in bean and Arabidopsis. Syringolin A-negative mutants, which induce stomatal closure, can be complemented by exogenous addition of not only syringolin A but also MG132, a well-characterized and structurally unrelated proteasome inhibitor. This demonstrates that proteasome activity is crucial for guard cell function. In Arabidopsis, stomatal immunity was salicylic acid (SA)-dependent and required NPR1, a key regulator of the SA-dependent defense pathway whose proteasome-dependent turnover has been reported to be essential for its function. Thus, elimination of NPR1 turnover through proteasome inhibition by syringolin A is an attractive hypothesis to explain the observed inhibition of stomatal immunity by syringolin A.

Syringolin A, an important virulence factor in the interaction of the phytopathogenic bacterium Pseudomonas syringae pv. syringae B728a with its host plant Phaseolus vulgaris (bean), was recently shown to irreversibly inhibit eukaryotic proteasomes by a novel mechanism. Syringolin A is synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase and consists of a tripeptide part including a twelve-membered ring with an N-terminal valine that is joined to a second valine via a very unusual ureido group. Analysis of sequence and architecture of the syringolin A synthetase gene cluster with the five open reading frames sylA-sylE allowed to formulate a biosynthesis model that explained all structural features of the tripeptide part of syringolin A but left the biosynthesis of the unusual ureido group unaccounted for.

Syringolin A, the product of a mixed non-ribosomal peptide/polyketide synthetase, is secreted by Pseudomonas syringae pv. syringae under in planta conditions and is one of the molecular determinants recognized by nonhost plant species. Spray application of syringolin A onto powdery mildew-infected wheat and Arabidopsis has the remarkable effect of reprogramming epidermal cells that are colonized by the powdery mildew fungi Blumeria graminis f. sp. tritici and Erysiphe cichoracearum, respectively, in a compatible interaction to undergo hypersensitive cell death. No hypersensitive cell death is observed if the compound is applied onto uninfected plants. Transcriptome analyses in wheat and Arabidopsis with regard to powdery mildew inoculation and/or syringolin A spraying lead to a hypothesis about how syringolin A may accomplish to induce the hypersensitive reaction (HR) in colonized cells. The model is supported by transcriptome analyis of an Arabidopsis mutant in which HR is not induced upon syringolin A spraying of powdery mildew-infected plants. Cloning of the syringolin A synthetase genes has allowed us to build a detailed model of syringolin A synthesis based on the gene structure. This model in turn enabled us to clone the genes responsible for the synthesis of glidobactins (syn. cepafungins), antibiotics with a structure related to syringolin A that were reported to have antitumor activity, from an unknown species belonging to the order Burkholderiales. Comparisons to the approximately 700 complete eubacterial genomic sequences known resulted in the identification of a small but very intriguing group of pathogenic bacteria postulated to produce glidobacting-like molecules.