法國和日本研究人員不久前發現一個與金黃色葡萄球菌產生耐藥性有關的基因，並探明該基因的表達機製。日前在美國學術期刊《科學公共圖書館病原卷》上。
金黃色葡萄球菌是一種常見病菌，能引起皮膚損傷、心內膜炎、急性肺炎、骨髓炎和敗血症等多種感染。針對抗生素產生多重耐藥性的此類病菌感染，比如對甲氧西林有耐藥性的金黃色葡萄球菌感染，已成為全球醫療衛生界麵臨的難題。研究人員對耐藥性金黃色葡萄球菌獲得耐藥基因的機製一直不甚了解。
來自法國巴斯德研究所、法國國家科研中心和日本築波大學的研究人員報告說，他們發現金黃色葡萄球菌中一個名為 sigH的基因表達能使該病菌啟動一種機製，從其他生物那裏“引進”特殊基因，並將其轉變為自己的耐藥基因。
此外，研究人員還探明了 sigH基因的兩種表達機製。在實驗中，研究人員通過激活 sigH基因，使普通金黃色葡萄球菌對甲氧西林產生耐藥性。
研究人員認為，這一發現有助於開發新療法，通過抑製特定基因的表達來消除這種病菌的耐藥性。
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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.
