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研究发现金葡菌耐药相关基因

来源:医学论坛网    时间:2012年11月05日    点击数:    5星

法国和日本研究人员不久前发现一个与金黄色葡萄球菌产生耐药性有关的基因,并探明该基因的表达机制。日前在美国学术期刊《科学公共图书馆病原卷》上。


金黄色葡萄球菌是一种常见病菌,能引起皮肤损伤、心内膜炎、急性肺炎、骨髓炎和败血症等多种感染。针对抗生素产生多重耐药性的此类病菌感染,比如对甲氧西林有耐药性的金黄色葡萄球菌感染,已成为全球医疗卫生界面临的难题。研究人员对耐药性金黄色葡萄球菌获得耐药基因的机制一直不甚了解。

来自法国巴斯德研究所、法国国家科研中心和日本筑波大学的研究人员报告说,他们发现金黄色葡萄球菌中一个名为 sigH 的基因表达能使该病菌启动一种机制,从其他生物那里“引进”特殊基因,并将其转变为自己的耐药基因。

此外,研究人员还探明了 sigH 基因的两种表达机制。在实验中,研究人员通过激活 sigH 基因,使普通金黄色葡萄球菌对甲氧西林产生耐药性。

研究人员认为,这一发现有助于开发新疗法,通过抑制特定基因的表达来消除这种病菌的耐药性。
相关链接:

Expression of a Cryptic Secondary Sigma Factor Gene Unveils Natural Competence for DNA Transformation in Staphylococcus aureus
Kazuya Morikawa1,2*, Aya J. Takemura1, Yumiko Inose1, Melody Tsai1, Le Thuy Nguyen Thi1, Toshiko Ohta1, Tarek Msadek2,3*

1 University of Tsukuba, Division of Biomedical Science, Faculty of Medicine, Tsukuba, Japan, 2 Institut Pasteur, Biology of Gram Positive Pathogens, Department of Microbiology, Paris, France, 3 CNRS ERL 3526, Paris, France

Abstract
It has long been a question whether Staphylococcus aureus, a major human pathogen, is able to develop natural competence for transformation by DNA. We previously showed that a novel staphylococcal secondary sigma factor, SigH, was a likely key component for competence development, but the corresponding gene appeared to be cryptic as its expression could not be detected during growth under standard laboratory conditions. Here, we have uncovered two distinct mechanisms allowing activation of SigH production in a minor fraction of the bacterial cell population. The first is a chromosomal gene duplication rearrangement occurring spontaneously at a low frequency [≤10−5], generating expression of a new chimeric sigH gene. The second involves post-transcriptional regulation through an upstream inverted repeat sequence, effectively suppressing expression of the sigH gene. Importantly, we have demonstrated for the first time that S. aureus cells producing active SigH become competent for transformation by plasmid or chromosomal DNA, which requires the expression of SigH-controlled competence genes. Additionally, using DNA from the N315 MRSA strain, we successfully transferred the full length SCCmecII element through natural transformation to a methicillin-sensitive strain, conferring methicillin resistance to the resulting S. aureus transformants. Taken together, we propose a unique model for staphylococcal competence regulation by SigH that could help explain the acquisition of antibiotic resistance genes through horizontal gene transfer in this important pathogen.

原文链接:http://www.cmt.com.cn/detail/92991.html

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