Deciphering small molecules as virulence factors by the bacterial sugarcane pathogen Xanthomonas albilineans

植物病原细菌为了在植物上成功定殖，进化出了多种毒力因子，以破坏寄主的防御或获取营养。这些致病过程的理解是特别重要的，因为细菌能够造成巨大的经济损失的作物。白纹黄单胞菌（Xanthomonasalbilineans，Xa）是一种系统性的木质部入侵病原菌，可引起甘蔗叶枯病，是甘蔗种间杂种的致死性病害。Xa-甘蔗病理系统是植物病理学中的原始模型，因为：（i）Xa被限制在木质部内，但疾病症状由薄壁组织细胞的变化引起;（ii）Xa感染可以在急性疾病发生之前潜伏数周或数月。Xa基因组的测序结果表明，缺乏III型分泌系统Hrp，而是表明，致病性是依赖于次生代谢产物的生物合成。最突出的代表是albicidin，这是一种引起叶枯症状的特异性毒素。此外，基因组测序结果表明存在编码另外三种非核糖体肽合成酶基因簇（Metacols A、B和C）的基因。次生代谢产物的产生意味着在Xa的发病机制中作为效应物或毒素的额外功能。因此，该项目旨在分离和结构阐明albicidin，其衍生物和次级代谢产物Metacols A-C。该研究将进一步旨在表征Metacols A-C的生物活性，以更好地了解X。albilineans在甘蔗木质部导管中成功传播。这项工作将产生影响的Xa-甘蔗致病系统的理解，也有两个其他的致病系统，涉及黄单胞菌属的物种，其中具有Metacol-B类NRPS基因簇（水稻病原体黄单胞菌和小麦病原体黄单胞菌）。最后，albicidin可能作为新型抗生素的先导结构。

In order to successfully colonize plants, plant pathogenic bacteria have evolved a variety of virulence factors to subvert host defences or to obtain nutrients. The understanding of these pathogenic processes is of particular importance since bacteria are capable of causing enormous economic losses on crop plants. Xanthomonas albilineans (Xa) is a systemic, xylem-invading pathogen that causes leaf scald, a lethal disease of sugarcane (Saccharum interspecific hybrids). The Xa-sugarcane pathosystem is an original model in plant pathology because: (i) Xa is constrained within the xylem, but disease symptoms result from changes in chlorenchyma cells; (ii) the Xa infection can be latent for many weeks or months before occurrence of acute disease. Sequencing of the genome of Xa revealed the absence of the type III secretion system Hrp and rather suggested that pathogenicity is dependent on the biosynthesis of secondary metabolites. The most prominent representative is albicidin, a specific toxin that causes foliar leaf scald symptoms. Furthermore, genome sequencing results indicate the presence of genes encoding for additional three non-ribosomal peptide synthetase gene clusters (Metacols A, B and C). The production of secondary metabolites implies additional functions as effectors or toxins in pathogenesis of Xa. Hence, the project is directed to the isolation and structure elucidation of albicidin, its derivatives and of secondary metabolites Metacols A-C. The study will further aim at the characterization of the bioactivities of Metacols A-C to better understand how X. albilineans successfully spreads in sugarcane xylem vessels. The work will have an impact on the understanding of the Xa-sugarcane pathosystem and also two other pathosystems involving species of Xanthomonas, which possess a Metacol-B like NRPS gene cluster (the rice pathogen Xanthomonas oryzae and the wheat pathogen Xanthomonas transluscens). Finally, albicidin may server as a lead structure for novel antibiotics.