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Infect. Immun. doi:10.1128/IAI.01007-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The MisR/MisS Two-Component Regulon in Neisseria meningitidis

Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Laboratories of Bacterial Pathogenesis, Department of Veterans Affairs Medical Center, Decatur, GA, USA; Discipline of Microbiology and Immunology, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Australia

^* To whom correspondence should be addressed. Email: ytzeng{at}emory.edu.

	Abstract

Two-component regulatory systems are involved in processes important for bacterial pathogenesis. Inactivation of the misR/misS system in Neisseria meningitidis results in 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/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 -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 MisRS 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 (EMSA) were carried out using purified MisR-6xHis protein. Among 22 genes examined, MisR directly interacted with fourteen 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/MisS 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.