Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity
Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity
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DOI：
10.1073/pnas.1523199113
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发表时间：
2016-06-28
影响因子：
11.1
通讯作者：
Palsson, Bernhard O.
中科院分区：
文献类型：
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作者：
Bosi, Emanuele;Monk, Jonathan M.;Palsson, Bernhard O.
金黄色葡萄球菌是一种卓越的细菌病原体，能够在其人类宿主内定殖多种生态位。本文基于64株金黄色葡萄球菌的基因组序列分析，描述了金黄色葡萄球菌的泛基因组，这些金黄色葡萄球菌跨越了一系列生态位、宿主类型和抗生素耐药谱。在此基础上，金黄色葡萄球菌预计将拥有由7411个基因组成的开放泛基因组和由1441个基因组成的核心基因组。代谢在该核心基因组中高度保守；然而，菌株之间的氨基酸和核苷酸生物合成途径存在差异。建立了64株金黄色葡萄球菌的基因组尺度代谢模型（GEMs）。这些GEMs使系统方法能够表征金黄色葡萄球菌物种的核心代谢和全代谢能力。预测所有模型对维生素烟酸（维生素B3）和维生素B1均为营养不良，而对核黄素（维生素B2）、鸟苷、亮氨酸、蛋氨酸和半胱氨酸等均为菌株特异性营养不良。利用GEMs系统分析了300多种不同生长支持环境下的生长能力。结果确定代谢能力与致病性状和毒力获得有关。这些特征可用于区分导致轻度和严重感染的菌株以及对宿主的偏好（例如，动物和人类）。因此，对一个物种的多个菌株进行基因组规模的分析可以用来确定毒力的代谢决定因素，并增加我们对这种致命病原体的某些菌株在世界各地迅速传播的理解。
Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus. These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world.