DNA adenine methylation regulates virulence gene expression in Salmonella enterica serovar typhimurium

DNA adenine methylation regulates virulence gene expression in Salmonella enterica serovar typhimurium
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DOI:
10.1128/jb.00847-06
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发表时间:
2006-12-01
影响因子:
3.2
通讯作者:
Casadesus, Josep
Casadesus, Josep
中科院分区:
生物学3区
文献类型:
--
作者:
Balbontin, Roberto;Rowley, Gary;Casadesus, Josep

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在Luria-Bertani培养基中生长期间,在肠道沙门氏菌鼠伤寒血清型菌株SL 1344和两种缺乏Dam甲基化酶的同基因衍生物中进行转录组学分析。更多的基因被抑制,而不是被激活的大坝甲基化(139对37)。Dam甲基化差异调节的关键基因被独立验证。Dam抑制基因的最大类别包括属于SOS调节子的基因,如先前在大肠杆菌中描述的,以及SOS诱导的沙门氏菌原噬菌体ST 64 B、Giffsy-1和Fels-2的基因。还鉴定了依赖于母鼠的毒性相关基因。Dam甲基化激活了致病岛SPI-1中的入侵基因,而Dam甲基化抑制了菌毛操纵子std。某些鞭毛基因被Dam甲基化抑制,而S.肠道显示出减少的运动性。在没有Dam甲基化的情况下,还发现趋化基因cheR(被Dam抑制)和STM3216(被Dam激活)以及Braun脂蛋白基因lppB(被Dam激活)的表达模式发生变化。在特定毒力基因的调节中需要DNA腺嘌呤甲基化,这表明沙门氏菌Dam突变体在小鼠模型中的某些缺陷可能是由基因表达模式的改变引起的。
Transcriptomic analyses during growth in Luria-Bertani medium were performed in strain SL1344 of Salmonella enterica serovar Typhimurium and in two isogenic derivatives lacking Dam methylase. More genes were repressed than were activated by Dam methylation (139 versus 37). Key genes that were differentially regulated by Dam methylation were verified independently. The largest classes of Dam-repressed genes included genes belonging to the SOS regulon, as previously described in Escherichia coli, and genes of the SOS-inducible Salmonella prophages ST64B, Gifsy-1, and Fels-2. Dam-dependent virulence-related genes were also identified. Invasion genes in pathogenicity island SPI-1 were activated by Dam methylation, while the fimbrial operon std was repressed by Dam methylation. Certain flagellar genes were repressed by Dam methylation, and Dam(-) mutants of S. enterica showed reduced motility. Altered expression patterns in the absence of Dam methylation were also found for the chemotaxis genes cheR (repressed by Dam) and STM3216 (activated by Dam) and for the Braun lipoprotein gene, lppB (activated by Dam). The requirement for DNA adenine methylation in the regulation of specific virulence genes suggests that certain defects of Salmonella Dam- mutants in the mouse model may be caused by altered patterns of gene expression.