Whole genome sequencing of meticillin-resistant Staphylococcus aureus
Whole genome sequencing of meticillin-resistant Staphylococcus aureus
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DOI：
10.1016/s0140-6736(00)04403-2
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发表时间：
2001-04-21
期刊：
影响因子：
168.9
通讯作者：
Hiramatsu, K
中科院分区：
文献类型：
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作者：
Kuroda, M;Ohta, T;Hiramatsu, K
背景金黄色葡萄球菌是社区获得性和医院获得性感染的主要原因之一。它产生许多毒素，包括引起独特疾病实体的超抗原，如中毒性休克综合征和葡萄球菌猩红热，并对几乎所有抗生素产生耐药性。全基因组分析是未来发展的对策，对该organis.Methods的全基因组序列测定的两个相关的金黄色葡萄球菌菌株（N315和Mu50）。N315是1982年分离的耐甲氧西林金黄色葡萄球菌（MRSA）菌株，Mu50是1997年分离的具有万古霉素耐药性的MRSA菌株。开放的阅读框架进行了鉴定，通过使用GAMBLER和GLIMMER程序，和注释的每一个都做了一个BLAST同源性搜索，基序分析，和蛋白定位predictions.Findings葡萄球菌基因组是由一个复杂的混合物的基因，其中许多似乎已获得横向基因转移。大多数抗生素抗性基因由质粒或移动的遗传元件携带，包括一个独特的抗性岛。在基因组中发现了三类新的致病岛：中毒性休克综合征毒素岛家族、外毒素岛和肠毒素岛。在后两个致病岛中，发现外毒素和肠毒素基因簇与编码推定致病因子的其他基因簇紧密相连。通过对基因组复杂性的观察和基因横向转移的证据，揭示了金黄色葡萄球菌从各种生物体中获得有用基因的显著能力。编码超级抗原的基因的重复复制解释了为什么金黄色葡萄球菌能够感染不同遗传背景的人，引发严重的免疫反应。对许多新发现的基因产物，包括70个推定的毒力因子的研究，将大大提高我们对葡萄球菌生物学和金黄色葡萄球菌引起的感染性疾病过程的理解。
Background Staphylococcus aureus is one of the major causes of community-acquired and hospital-acquired infections. It produces numerous toxins including superantigens that cause unique disease entities such as toxic-shock syndrome and staphylococcal scarlet fever, and has acquired resistance to practically all antibiotics. Whole genome analysis is a necessary step towards future development of countermeasures against this organism.Methods Whole genome sequences of two related S aureus strains (N315 and Mu50) were determined by shot-gun random sequencing. N315 is a meticillin-resistant S aureus (MRSA) strain isolated in 1982, and Mu50 is an MRSA strain with vancomycin resistance isolated in 1997. The open reading frames were identified by use of GAMBLER and GLIMMER programs, and annotation of each was done with a BLAST homology search, motif analysis, and protein localisation prediction.Findings The Staphylococcus genome was composed of a complex mixture of genes, many of which seem to have been acquired by lateral gene transfer. Most of the antibiotic resistance genes were carried either by plasmids or by mobile genetic elements including a unique resistance island. Three classes of new pathogenicity islands were identified in the genome: a toxic-shock-syndrome toxin island family, exotoxin islands, and enterotoxin islands. in the latter two pathogenicity islands, clusters of exotoxin and enterotoxin genes were found closely linked with other gene clusters encoding putative pathogenic factors. The analysis also identified 70 candidates for new virulence factors.Interpretation The remarkable ability of S aureus to acquire useful genes from various organisms was revealed through the observation of genome complexity and evidence of lateral gene transfer. Repeated duplication of genes encoding superantigens explains why S aureus is capable of infecting humans of diverse genetic backgrounds, eliciting severe immune reactions. Investigation of many newly identified gene products, including the 70 putative virulence factors, will greatly improve our understanding of the biology of staphylococci and the processes of infectious diseases caused by S aureus.