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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance.
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Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance.

机译:两个临床金黄色葡萄球菌菌株的完整基因组:毒力和耐药性快速进化的证据。

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摘要

Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximately 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: approximately 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC(476)), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.
机译:金黄色葡萄球菌是重要的医院和社区获得性病原体。它的遗传可塑性促进了许多有毒力和耐药性菌株的进化,带来了重大且不断变化的临床挑战。我们对分离自不同临床背景的两种致病性金黄色葡萄球菌菌株的大约2.8 Mbp基因组进行了测序:最近流行的耐甲氧西林金黄色葡萄球菌EMRSA-16克隆(MRSA252)在医院获得的代表,这在临床上很重要,全球流行的血统;以及获得的侵入性社区获得的对甲氧西林敏感的金黄色葡萄球菌克隆(MSSA476)的代表。比较基因组学方法用于探索临床上重要的金黄色葡萄球菌基因组进化的机制,并确定影响毒力和耐药性的区域。 MRSA252和MSSA476的基因组序列具有一个保守的核心区域,但其辅助遗传元件存在显着差异。 MRSA252是迄今测序最多的遗传多样性最广的金黄色葡萄球菌菌株:与其他已发表的基因组相比,约有6%的基因组是新颖的,并且它包含几个独特的遗传元件。 MSSA476对甲氧西林敏感,但它包含一种新型葡萄球菌染色体盒(SCC)mec样元件(命名为SCC(476)),该元件与MRSA菌株中SCCmec元件整合在染色体的同一位点,但编码假定的融合蛋白耐酸性蛋白。通过比较MSSA476基因组和与MRSA社区极为密切相关的菌株,可以清楚地说明辅助元素在金黄色葡萄球菌快速进化中的关键作用。携带毒力和耐药性决定因素的大型活动元件的差异分布可能是这些菌株在临床上重要的表型差异的原因。

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