Transcriptional regulation of subclass 5b fimbriae.
Transcriptional regulation of subclass 5b fimbriae.
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DOI：
10.1186/1471-2180-8-180
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发表时间：
2008-10-14
期刊：
影响因子：
4.2
通讯作者：
Munson, George P.
中科院分区：
文献类型：
--
作者：
Bodero, Maria D.;Harden, Elizabeth A.;Munson, George P.
产肠毒素大肠杆菌(ETEC)是发展中国家婴幼儿死亡的主要原因。这种肠道病原体通过产生一种或多种肠毒素，使真核细胞中毒，最终导致肠腔失水，从而导致大量水样腹泻。毒力也依赖于菌毛粘附素，这种粘附素有助于小肠的定植。CS1菌毛的表达受RNS的正调控，RNS是AraC/XylS超家族转录调控因子的成员。根据菌毛蛋白同源性，CS1菌毛与CS17、CS19和PCFO71菌毛一起被归类为5b亚类。在这项研究中，我们发现RNS正向调节这些亚类5b成员的表达。DNase I足迹显示在每个菌毛启动子的-35六聚体附近有一个RNS结合位点。CS17和PCFO71菌毛启动子携带以-109.5为中心的第二个RNS结合位点，相对于依赖RNS的转录起始点。第二个结合位点位于CS19启动子的-108.5。任何一个位点的突变都减少了每个启动子依赖RNS的转录，这表明与这些位点结合的分子显然相互独立地发挥作用，每个分子都对菌毛启动子的激活具有相加作用。本研究证明ETEC毒力调节因子RNS是所有已知5b菌毛表达所必需的。由于RNS还可以控制其他ETEC菌毛的表达，包括5a和5c亚类的菌毛，因此RNS的失活或抑制可能是预防ETEC感染的有效策略。
Enterotoxigenic Escherichia coli (ETEC) is a major cause of infant and child mortality in developing countries. This enteric pathogen causes profuse watery diarrhea by elaborating one or more enterotoxins that intoxicate eukaryotic cells and ultimately leads to a loss of water to the intestinal lumen. Virulence is also dependent upon fimbrial adhesins that facilitate colonization of the small intestine. The expression of CS1 fimbriae is positively regulated by Rns, a member of the AraC/XylS superfamily of transcriptional regulators. Based on fimbrial protein homology, CS1 fimbriae have been categorized as subclass 5b along with CS17, CS19, and PCFO71 fimbriae. In this study we show that Rns positively regulates the expression of these other subclass 5b members. DNase I footprinting revealed a Rns binding site adjacent to the -35 hexamer of each fimbrial promoter. The CS17 and PCFO71 fimbrial promoters carry a second Rns binding site centered at -109.5, relative to the Rns-dependent transcription start site. This second binding site is centered at -108.5 for the CS19 promoter. Mutagenesis of either site reduced Rns-dependent transcription from each promoter indicating that the molecules bound to these sites apparently function independently of one another, with each having an additive effect upon fimbrial promoter activation. This study demonstrates that the ETEC virulence regulator Rns is required for the expression of all known 5b fimbriae. Since Rns is also known to control the expression of additional ETEC fimbriae, including those within subclasses 5a and 5c, the inactivation or inhibition of Rns could be an effective strategy to prevent ETEC infections.
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影响因子：
3.2
作者：
Pilonieta, M. Carolina;Bodero, Maria D.;Munson, George P.
通讯作者：
Munson, George P.
影响因子：
3.1
作者：
Anantha, RP;McVeigh, AL;Savarino, SJ
通讯作者：
Savarino, SJ
影响因子：
3.6
作者：
Sakellaris, H;Balding, DP;Scott, JR
通讯作者：
Scott, JR
影响因子：
56.9
作者：
Hung, DT;Shakhnovich, EA;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
3.1
作者：
CARON, J;SCOTT, JR
通讯作者：
SCOTT, JR