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Autoregulation of the MisR/MisS Two-Component Signal Transduction System in Neisseria meningitidis

Yih-Ling Tzeng,^1* Xiaoliu Zhou,¹ Shaojia Bao,¹ Shuming Zhao,¹ Corie Noble,^2, and David S. Stephens^1,2

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia,¹ Laboratories of Microbial Pathogenesis, Department of Veterans Affairs Medical Center, Decatur, Georgia²

Received 20 February 2006/ Accepted 27 April 2006

Two-component regulatory systems are involved in processes important for bacterial pathogenesis. The proposed misR/misS (or phoP/phoQ) system is one of four two-component systems of the obligate human pathogen Neisseria meningitidis. Inactivation of this system results in loss of phosphorylation of the lipooligosaccharide inner core and causes attenuation in a mouse model of meningococcal infection. MisR and the cytoplasmic domain of MisS were purified as His₆ and maltose binding protein fusion proteins, respectively. The MisS fusion was shown to be autophosphorylated in the presence of ATP, and the phosphoryl group was subsequently transferred to MisR. The phosphotransfer reaction was halted with a MisR/D52A mutation, while a MisS/H246A mutation prevented autophosphorylation. Specific interaction of phosphorylated MisR (MisRP) and MisR with the misR promoter was demonstrated by gel mobility shift assays, where MisRP exhibited higher affinity than did the nonphosphorylated protein. The transcriptional start site of the misRS operon was mapped, and DNase I protection assays revealed that MisR interacted with a 15-bp region upstream of the transcriptional start site that shared no similarity to binding motifs of other two-component systems. Transcriptional reporter studies suggested that MisR phosphorylation is critical for the autoinduction of the misRS operon. Limited Mg²⁺ concentration failed to induce expression of the misRS operon, which is the only operon now proven to be under the direct control of the MisRS two-component system. Thus, these results indicate that the meningococcal MisRS system constitutes a functional signal transduction circuit and that both components are critical in the autoregulation of their expression.

Supplemental material for this article may be found at http://jb.asm.org/.

Present address: Mercer University School of Medicine, Macon, Ga.

This article has been cited by other articles:

• Tzeng, Y.-L., Kahler, C. M., Zhang, X., Stephens, D. S. (2008). MisR/MisS Two-Component Regulon in Neisseria meningitidis. Infect. Immun. 76: 704-716 [Abstract] [Full Text]  
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