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

为了成功地在植物上定殖，植物病原菌进化出多种毒力因子来破坏寄主防御或获取营养。了解这些致病过程特别重要，因为细菌能够给作物造成巨大的经济损失。摘要白色黄单胞菌(Xanthomonas albilineans，Xa)是一种侵染木质部的系统性病原菌，可引起甘蔗(Saccharum Inter种间杂交种)叶烫伤。Xa-甘蔗病理系统是植物病理学中的一个原始模型，因为：(I)Xa局限于木质部，但疾病症状是由绿色组织细胞的变化引起的；(Ii)Xa侵染在急性病害发生之前可能潜伏数周或数月。对Xa的基因组测序表明，Xa不存在III型分泌系统HRP，而是表明致病性依赖于次生代谢物的生物合成。最突出的代表是白化菌素，这是一种导致叶片烫伤症状的特殊毒素。此外，基因组测序结果表明，存在编码另外三个非核糖体多肽合成酶基因簇(Metacol A、B和C)的基因。次生代谢物的产生意味着在Xa的发病机制中具有作为效应物或毒素的额外功能。因此，该项目致力于白念珠菌素及其衍生物和次生代谢物Metacol A-C的分离和结构鉴定。这项研究将进一步研究Metacol A-C的生物活性，以更好地了解白纹伊蚊是如何在甘蔗木质部导管中成功传播的。这项工作将对了解Xa-甘蔗的病理系统以及另外两个涉及Xanthomonas物种的病理系统产生影响，这些Xanthomonas物种拥有一个类似于Metacol-B的NRPS基因簇(水稻Xanthomonas oryzae和小麦Xanthomonas Transluscens)。最后，白念珠菌素可能成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.