Genome-scale analysis of Methicillin-resistant Staphylococcus aureus USA300 reveals a tradeoff between pathogenesis and drug resistance.
Genome-scale analysis of Methicillin-resistant Staphylococcus aureus USA300 reveals a tradeoff between pathogenesis and drug resistance.
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DOI：
10.1038/s41598-018-20661-1
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发表时间：
2018-02-02
影响因子：
4.6
通讯作者：
Cho BK
中科院分区：
文献类型：
--
作者：
Choe D;Szubin R;Dahesh S;Cho S;Nizet V;Palsson B;Cho BK
金黄色葡萄球菌感染是一个日益严重的公共卫生威胁。金黄色葡萄球菌被认为具有精心设计的调控网络来协调其毒性。尽管它的重要性，系统的理解金黄色葡萄球菌的转录景观是有限的。在这里，我们描述了社区获得性耐甲氧西林金黄色葡萄球菌流行USA300分离物的主要转录组景观。我们通过实验确定了1861个转录起始位点及其主要启动子元件，包括高度保守的-35和-10元件，弱保守的-16元件和含有富含ag的sheen - dalgarno序列的5 '未翻译区域。此外，我们鉴定出225个基因的转录是从多个转录起始位点开始的，这表明在转录水平上具有潜在的调控功能。通过整合初级转录组分析和操纵子预测得到转录单元结构，差异基因表达的测量揭示了毒力调节因子Agr、sara家族转录调节因子和β-内酰胺抗性调节因子的调控框架。有趣的是，我们观察到毒力调节、β-内酰胺耐药性和代谢之间存在复杂的相互作用，这表明USA300菌株的发病机制和耐药性之间可能存在权衡。我们的研究结果为研究金黄色葡萄球菌的转录起始位置和深入了解其发病机制、毒力和耐药性的转录调控提供了平台资源。
Staphylococcus aureus infection is a rising public health care threat. S. aureus is believed to have elaborate regulatory networks that orchestrate its virulence. Despite its importance, the systematic understanding of the transcriptional landscape of S. aureus is limited. Here, we describe the primary transcriptome landscape of an epidemic USA300 isolate of community-acquired methicillin-resistant S. aureus. We experimentally determined 1,861 transcription start sites with their principal promoter elements, including well-conserved -35 and -10 elements and weakly conserved -16 element and 5′ untranslated regions containing AG-rich Shine-Dalgarno sequence. In addition, we identified 225 genes whose transcription was initiated from multiple transcription start sites, suggesting potential regulatory functions at transcription level. Along with the transcription unit architecture derived by integrating the primary transcriptome analysis with operon prediction, the measurement of differential gene expression revealed the regulatory framework of the virulence regulator Agr, the SarA-family transcriptional regulators, and β-lactam resistance regulators. Interestingly, we observed a complex interplay between virulence regulation, β-lactam resistance, and metabolism, suggesting a possible tradeoff between pathogenesis and drug resistance in the USA300 strain. Our results provide platform resource for the location of transcription initiation and an in-depth understanding of transcriptional regulation of pathogenesis, virulence, and antibiotic resistance in S. aureus.
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影响因子：
4.4
作者：
Babski J;Haas KA;Näther-Schindler D;Pfeiffer F;Förstner KU;Hammelmann M;Hilker R;Becker A;Sharma CM;Marchfelder A;Soppa J
通讯作者：
Soppa J
影响因子：
16.6
作者：
Jeong Y;Kim JN;Kim MW;Bucca G;Cho S;Yoon YJ;Kim BG;Roe JH;Kim SC;Smith CP;Cho BK
通讯作者：
Cho BK
小非编码 RNA：细胞内细菌病原体调节宿主免疫反应的新见解。
影响因子：
7.3
作者：
Ahmed W;Zheng K;Liu ZF
通讯作者：
Liu ZF
影响因子：
14.9
作者：
Chabelskaya S;Bordeau V;Felden B
通讯作者：
Felden B
影响因子：
4.8
作者：
Bischler, Thorsten;Tan, Hock Siew;Sharma, Cynthia M.
通讯作者：
Sharma, Cynthia M.