Institut für Genomforschung und Systembiologie, Centrum für Biotechnologie, Universität Bielefeld, Bielefeld, Germany.
BMC Genomics. 2010 Dec 30;11:728. doi: 10.1186/1471-2164-11-728.
Corynebacterium pseudotuberculosis is generally regarded as an important animal pathogen that rarely infects humans. Clinical strains are occasionally recovered from human cases of lymphadenitis, such as C. pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12-year-old girl with necrotizing lymphadenitis. To detect potential virulence factors and corresponding gene-regulatory networks in this human isolate, the genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing and functionally annotated.
Sequencing and assembly of the C. pseudotuberculosis FRC41 genome yielded a circular chromosome with a size of 2,337,913 bp and a mean G+C content of 52.2%. Specific gene sets associated with iron and zinc homeostasis were detected among the 2,110 predicted protein-coding regions and integrated into a gene-regulatory network that is linked with both the central metabolism and the oxidative stress response of FRC41. Two gene clusters encode proteins involved in the sortase-mediated polymerization of adhesive pili that can probably mediate the adherence to host tissue to facilitate additional ligand-receptor interactions and the delivery of virulence factors. The prominent virulence factors phospholipase D (Pld) and corynebacterial protease CP40 are encoded in the genome of this human isolate. The genome annotation revealed additional serine proteases, neuraminidase H, nitric oxide reductase, an invasion-associated protein, and acyl-CoA carboxylase subunits involved in mycolic acid biosynthesis as potential virulence factors. The cAMP-sensing transcription regulator GlxR plays a key role in controlling the expression of several genes contributing to virulence.
The functional data deduced from the genome sequencing and the extended knowledge of virulence factors indicate that the human isolate C. pseudotuberculosis FRC41 is equipped with a distinct gene set promoting its survival under unfavorable environmental conditions encountered in the mammalian host.
棒状杆菌通常被认为是一种重要的动物病原体,很少感染人类。临床菌株偶尔会从人类淋巴结炎病例中分离出来,例如从一名患有坏死性淋巴结炎的 12 岁女孩腹股沟淋巴结中分离出的假结核棒状杆菌 FRC41。为了检测该人类分离株中潜在的毒力因子和相应的基因调控网络,通过焦磷酸测序和功能注释确定了假结核棒状杆菌 FRC41 的基因组序列。
对假结核棒状杆菌 FRC41 基因组的测序和组装产生了一个大小为 2,337,913 bp 的圆形染色体,平均 G+C 含量为 52.2%。在 2,110 个预测的蛋白质编码区中检测到与铁和锌稳态相关的特定基因集,并将其整合到一个基因调控网络中,该网络与 FRC41 的中心代谢和氧化应激反应相关联。两个基因簇编码参与黏附性菌毛的Sortase 介导聚合的蛋白,这些菌毛可能介导对宿主组织的附着,以促进其他配体-受体相互作用和毒力因子的传递。该人类分离株的基因组中编码了显著的毒力因子磷脂酶 D (Pld)和棒状杆菌蛋白酶 CP40。基因组注释揭示了其他丝氨酸蛋白酶、神经氨酸酶 H、一氧化氮还原酶、与侵袭相关的蛋白和参与分枝菌酸生物合成的酰基辅酶 A 羧化酶亚基作为潜在的毒力因子。cAMP 感应转录调节因子 GlxR 在控制参与毒力的几个基因的表达中起关键作用。
从基因组测序中推导的功能数据和扩展的毒力因子知识表明,人类分离株假结核棒状杆菌 FRC41 配备了一组独特的基因,这些基因有助于其在哺乳动物宿主中遇到的不利环境条件下生存。