== From DNase I footprinting analysis, we identified three HexR binding sites. showed that HexR binds to the promoters of the central metabolic operons of the bacterium. Based on DNA sequence alignment of the target sites, we propose a 17-bp pseudopalindromic consensus HexR binding motif. Furthermore, N. meningitidisstrains lackinghexRexpression were deficient in establishing successful bacteremia in an infant rat model of infection, indicating the importance of this regulator for the survival of this pathogenin festn. IMPORTANCENeisseria meningitidisgrows on a limited range of nutrients during infection. We analyzed the gene expression ofN. (R)-CE3F4 meningitidisin response to glucose, the main energy source available in human blood, and we found that glucose regulates many genes implicated in energy metabolism and nutrient transport, as well as some implicated in virulence. We identified and characterized a transcriptional regulator (HexR) that controls metabolic genes ofN. meningitidisin response to glucose. We generated a mutant lacking HexR and found that the mutant was impaired in causing systemic infection in pet models. SinceN. meningitidislacks known bacterial regulators of energy metabolism, our findings suggest that HexR plays a major role in its biology by regulating metabolism in response to environmental signals. == INTRO == Neisseria meningitidisis a leading cause of meningitis and fulminant septicemia and is a significant public health problem, affecting mainly children and young adults. The annual number of invasive disease cases worldwide is estimated to be at least 1 . 2 million, with 135, 000 deaths related (R)-CE3F4 to invasive meningococcal disease (1, Rabbit Polyclonal to OR4L1 2). Meningococci are classified into 12 serogroups on the basis of the structure of the polysaccharide capsule; nearly all invasive meningococcal infections are caused by serogroups A, B, C, W, Y, and X (3). N. meningitidisis an encapsulated Gram-negative diplococcal bacterium and a (R)-CE3F4 (R)-CE3F4 strictly human pathogen. It colonizes about 3 to 30% of the human population, where it resides asymptomatically in the nasopharynx, its only known reservoir (4). For reasons not yet fully understood, some strains ofN. meningitidisare able to cross the mucosal epithelium and enter the bloodstream, where they evade immune killing by undergoing antigenic variance, by expressing surface antigens that mimic host molecules, and by recruiting human complement regulators (57). Furthermore, this pathogen can cross the blood-brain barrier and multiply in the cerebrospinal fluid, causing meningitis (8). Meningococcal adaptation to the different human host niches also occurs at the level of the metabolism (9), and the acquisition of (R)-CE3F4 nutrients that enable the bacterium to sustain growth and to multiply rapidly, causing septicemia, is critical intended for the outcome of meningococcal disease. N. meningitidisis thus able of adapting to different anatomical compartments of the host, including the nasopharyngeal mucosa, the bloodstream, and the subarachnoid compartment (10), where the available key nutrients, such as carbon sources, are diverse. Moreover, this bacteria can start using a restricted various substrates, just like glucose, lactate, or pyruvate, as main carbon options to allow expansion (1113). Sugar is the main carbon origin in blood vessels and cerebrospinal fluid (14), the two key host markets of condition; therefore , sugar constitutes a critical carbon origin forN. meningitidis. Accordingly, regarding one-half for the genes that happen to be essential for systemic infection encode enzymes that happen to be involved in the metabolic rate and carry of nutrition (15). Additionally , several environmental signals experience effects relating to the transcriptional regulations ofN. meningitidisduring host attacks, as found for straightener (16, 17), zinc.