Identification of Point Mutations in Clinical Staphylococcus aureus Strains That Produce Small-Colony Variants Auxotrophic for Menadione

Identification of Point Mutations in Clinical Staphylococcus aureus Strains That Produce Small-Colony Variants Auxotrophic for Menadione
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DOI:
10.1128/iai.01487-13
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发表时间:
2014-04-01
影响因子:
3.1
通讯作者:
Musser, James M.
Musser, James M.
中科院分区:
医学2区
文献类型:
--
作者:
Dean, Melissa A.;Olsen, Randall J.;Musser, James M.

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金黄色葡萄球菌(Staphylococcus aureus)小菌落变异株(SCVs)是一种慢性和复发性感染的致病菌,其致病机制和毒力作用至今尚未完全阐明。我们对五个S.金黄色葡萄球菌SCV菌株从人类患者中回收,并在甲萘醌生物合成途径中编码蛋白质的三个基因中发现了先前未鉴定的非同义点突变。遗传回复突变和野生型等位基因互补的分析证实,这些突变引起SCV表型和小鼠的毒力下降。
Staphylococcus aureus small-colony variants (SCVs) are implicated in chronic and relapsing infections that are difficult to diagnose and treat. Despite many years of study, the underlying molecular mechanisms and virulence effect of the small-colony phenotype remain incompletely understood. We sequenced the genomes of five S. aureus SCV strains recovered from human patients and discovered previously unidentified nonsynonymous point mutations in three genes encoding proteins in the menadione biosynthesis pathway. Analysis of genetic revertants and complementation with wild-type alleles confirmed that these mutations caused the SCV phenotype and decreased virulence for mice.