Ieva Raffaele, Alaimo Cristina, Delany Isabel, Spohn Gunther, Rappuoli Rino, Scarlato Vincenzo
Biochemistry and Molecular Biology Unit, Chiron Vaccines, 53100 Siena, Italy.
J Bacteriol. 2005 May;187(10):3421-30. doi: 10.1128/JB.187.10.3421-3430.2005.
The crgA gene of Neisseria meningitidis, which codes for a LysR-type regulator, is divergently oriented with respect to the mdaB gene, which codes for a hypothetical NADPH-quinone oxidoreductase. Transcriptional studies of the intergenic region between crgA and mdaB showed that two overlapping and divergent promoters, P(crgA) and P(mdaB), control transcription of these genes. Deletion of the crgA gene led to a strong increase in transcription from the P(crgA) promoter and a concomitant strong decrease in transcription from the P(mdaB) promoter, indicating that CrgA acts both as an autorepressor of transcription at its own promoter and as an activator of transcription at the mdaB promoter. Addition of alpha-methylene-gamma-butyrolactone (MBL), an inducer of NADPH-quinone oxidoreductase, to wild-type N. meningitidis cells specifically resulted in further activation of transcription of the P(mdaB) promoter and more repression of transcription of the P(crgA) promoter. No such regulation was observed when MBL was added to crgA-deficient cells, indicating that the transcriptional response to MBL is CrgA mediated. Under the same experimental conditions, no regulation of transcription by either CrgA or MBL was detected at the pilus and capsule genes. The role of CrgA in the regulation of gene expression during the infectious cycle of N. meningitidis is discussed.
脑膜炎奈瑟菌的crgA基因编码一种LysR型调节因子，它与编码假定的NADPH-醌氧化还原酶的mdaB基因呈反向排列。对crgA和mdaB之间基因间区域的转录研究表明，两个重叠且反向的启动子P(crgA)和P(mdaB)控制着这些基因的转录。crgA基因的缺失导致P(crgA)启动子的转录大幅增加，同时P(mdaB)启动子的转录大幅减少，这表明CrgA在其自身启动子处既作为转录的自动抑制因子，又在mdaB启动子处作为转录的激活因子发挥作用。向野生型脑膜炎奈瑟菌细胞中添加α-亚甲基-γ-丁内酯（MBL，一种NADPH-醌氧化还原酶的诱导剂），特异性地导致P(mdaB)启动子的转录进一步激活，以及P(crgA)启动子的转录更多地受到抑制。当将MBL添加到缺乏crgA的细胞中时，未观察到这种调节，这表明对MBL的转录反应是由CrgA介导的。在相同的实验条件下，在菌毛和荚膜基因处未检测到CrgA或MBL对转录的调节。本文讨论了CrgA在脑膜炎奈瑟菌感染周期中基因表达调控中的作用。
