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Infection and Immunity, February 2008, p. 704-716, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01007-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

MisR/MisS Two-Component Regulon in Neisseria meningitidis{triangledown} ,{dagger}

Yih-Ling Tzeng,1* Charlene M. Kahler,3 Xinjian Zhang,1,{ddagger} and David S. Stephens1,2

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia,1 Laboratories of Bacterial Pathogenesis, Department of Veterans Affairs Medical Center, Decatur, Georgia,2 Discipline of Microbiology and Immunology, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Perth, Australia3

Received 23 July 2007/ Returned for modification 6 September 2007/ Accepted 20 November 2007

Two-component regulatory systems are involved in processes important for bacterial pathogenesis. Inactivation of the misR/misS system in Neisseria meningitidis results in the loss of phosphorylation of the lipooligosaccharide inner core and causes attenuation in a mouse model of meningococcal infection. One hundred seventeen (78 up-regulated and 39 down-regulated) potential regulatory targets of the MisR/MisS (MisR/S) system were identified by transcriptional profiling of the NMBmisR mutant and the parental wild-type meningococcal strain NMB. The regulatory effect was further confirmed in a subset of target genes by quantitative real-time PCR and β-galactosidase transcriptional fusion reporter assays. The MisR regulon includes genes encoding proteins necessary for protein folding in the bacterial cytoplasm and periplasm, transcriptional regulation, metabolism, iron assimilation, and type I protein transport. Mutation in the MisR/S system caused increased sensitivity to oxidative stress and also resulted in decreased susceptibility to complement-mediated killing by normal human serum. To identify the direct targets of MisR regulation, electrophoretic mobility shift assays were carried out using purified MisR-His6 protein. Among 22 genes examined, misR directly interacted with 14 promoter regions. Six promoters were further investigated by DNase I protection assays, and a MisR-binding consensus sequence was proposed. Thus, the direct regulatory targets of MisR and the minimal regulon of the meningococcal MisR/S two-component signal transduction system were characterized. These data indicate that the MisR/S system influences a wide range of biological functions in N. meningitidis either directly or via intermediate regulators.

* Corresponding author. Mailing address: Woodruff Memorial Research Building, Room 2101, 1639 Pierce Drive, Atlanta, GA 30322. Phone: (404) 727-8393. Fax: (404) 712-2278. E-mail: ytzeng{at}emory.edu

{triangledown} Published ahead of print on 3 December 2007.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: V. J. DiRita

{ddagger} Present address: Department of Chemistry, Georgia State University, Atlanta, GA.

Infection and Immunity, February 2008, p. 704-716, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01007-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jamet, A., Rousseau, C., Monfort, J.-B., Frapy, E., Nassif, X., Martin, P. (2009). A two-component system is required for colonization of host cells by meningococcus. Microbiology 155: 2288-2295 [Abstract] [Full Text]  
  • Sannigrahi, S., Zhang, X., Tzeng, Y.-L. (2009). Regulation of the type I protein secretion system by the MisR/MisS two-component system in Neisseria meningitidis. Microbiology 155: 1588-1601 [Abstract] [Full Text]  


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