背景:长期以来,细菌致病性对患者护理造成严重影响。铜绿假单胞菌是医院获得性感染和医院疾病的常见原因。已知通过群体感应和外毒素的产生定殖感染宿主。
方法:目前的工作是分析铜绿假单胞菌PAO1引起的蛋白质组学改变,以研究群体感应抑制剂6-甲基香豆素对秀丽隐杆线虫模型中PAO1感染性的影响。
结果:通过基于串联质量标签的定量蛋白质组学方法,发现229种蛋白质在感染和抑制时受到差异调节。其中,发现34种蛋白质在感染和群体感应抑制条件下都失调。随着参与宿主-病原体相互作用的蛋白质的失调,发现PAO1可诱导核糖体失活应激,并伴有线粒体蛋白的下调。这又导致细胞凋亡的失调。参与核糖体生物发生和结构的多种蛋白的表达,氧化磷酸化,和线粒体酶因感染而改变。这个机制,由PAO1适应在宿主中生存,通过挽救核糖体和线粒体蛋白的下调而被6-甲基香豆素抑制。
结论:综合来看,数据反映了由于群体感应引起的分子改变以及抑制剂在控制发病机制中的有用性。
BACKGROUND: Bacterial pathogenicity has for long posed severe effects on patient care. Pseudomonas aeruginosa is a common cause of hospital-acquired infections and nosocomial illnesses. It is known to infect the host by colonizing through quorum sensing and the production of exotoxins.
METHODS: The current effort is an analysis of proteomic alterations caused by P. aeruginosa PAO1 to study the effects of quorum sensing inhibitor 6-Methylcoumarin on PAO1 infectivity in the Caenorhabditis elegans model.
RESULTS: Through tandem mass tag-based quantitative proteomics approaches, 229 proteins were found to be differentially regulated in infection and upon inhibition. Among these, 34 proteins were found to be dysregulated in both infection and quorum-sensing inhibition conditions. Along with the dysregulation of proteins involved in host-pathogen interaction, PAO1 was found to induce ribosome-inactivating stress accompanied by the downregulating mitochondrial proteins. This in turn caused dysregulation of apoptosis. The expression of multiple proteins involved in ribosome biogenesis and structure, oxidative phosphorylation, and mitochondrial enzymes were altered due to infection. This mechanism, adapted by PAO1 to survive in the host, was inhibited by 6-Methylcoumarin by rescuing the downregulation of ribosomal and mitochondrial proteins.
CONCLUSIONS: Taken together, the data reflect the molecular alterations due to quorum sensing and the usefulness of inhibitors in controlling pathogenesis.