Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2009 Sep 25;4(9):e7167. doi: 10.1371/journal.pone.0007167.
Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design.
鉴定新的毒力因子对于理解细菌发病机制和设计抗菌策略至关重要。在本研究中,我们在变形菌门中发现了这样一个因子,称为 KerV。在多种真核宿主感染模型中进行的实验表明,当铜绿假单胞菌 kerV 缺失突变体与变形虫、植物、苍蝇和老鼠相互作用时,其毒力受到损害。生物信息学分析表明,KerV 是一种假定的甲基转移酶,在许多变形菌中都得到很好的保守,包括许多知名和新兴的病原体(例如,毒力较强的伯克霍尔德菌、大肠杆菌、志贺氏菌、弧菌、沙门氏菌、耶尔森氏菌和布鲁氏菌属)。此外,在本研究中分析的 197 个 KerV 直系同源物中,约 89%存在于一个定义明确的基因组邻近区域,该区域还具有必需的 DNA 复制和修复基因以及解毒基因。最后,用缺失突变体感染黑腹果蝇表明,KerV 直系同源物在霍乱弧菌和假结核耶尔森菌的发病机制中也很关键。我们的研究结果表明,KerV 作为一种毒力因子,在致病性变形菌中具有新的广泛意义,它可能成为抗生素药物设计的新靶标。