{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:24:10Z","timestamp":1792185850734,"version":"4.4.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T00:00:00Z","timestamp":1455494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2016,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria meningitidis<\/jats:named-content>\n            , an exclusively human pathogen and the leading cause of bacterial meningitis, must adapt to different host niches during human infection.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>\n            can utilize a restricted range of carbon sources, including lactate, glucose, and pyruvate, whose concentrations vary in host niches. Microarray analysis of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>\n            grown in a chemically defined medium in the presence or absence of glucose allowed us to identify genes regulated by carbon source availability. Most such genes are implicated in energy metabolism and transport, and some are implicated in virulence. In particular, genes involved in glucose catabolism were upregulated, whereas genes involved in the tricarboxylic acid cycle were downregulated. Several genes encoding surface-exposed proteins, including the MafA adhesins and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria<\/jats:named-content>\n            surface protein A, were upregulated in the presence of glucose. Our microarray analysis led to the identification of a glucose-responsive\n            <jats:italic>hexR<\/jats:italic>\n            -like transcriptional regulator that controls genes of the central carbon metabolism of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>\n            in response to glucose. We characterized the HexR regulon and showed that the\n            <jats:italic>hexR<\/jats:italic>\n            gene is accountable for some of the glucose-responsive regulation;\n            <jats:italic>in vitro<\/jats:italic>\n            assays with the purified protein 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            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>\n            strains lacking\n            <jats:italic>hexR<\/jats:italic>\n            expression were deficient in establishing successful bacteremia in an infant rat model of infection, indicating the importance of this regulator for the survival of this pathogen\n            <jats:italic>in vivo<\/jats:italic>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria meningitidis<\/jats:named-content>\n            grows on a limited range of nutrients during infection. We analyzed the gene expression of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>\n            in 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 of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>\n            in response to glucose. We generated a mutant lacking HexR and found that the mutant was impaired in causing systemic infection in animal models. Since\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. meningitidis<\/jats:named-content>\n            lacks 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.\n          <\/jats:p>","DOI":"10.1128\/jb.00659-15","type":"journal-article","created":{"date-parts":[[2015,12,8]],"date-time":"2015-12-08T15:05:40Z","timestamp":1449587140000},"page":"644-654","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["HexR Controls Glucose-Responsive Genes and Central Carbon Metabolism in Neisseria meningitidis"],"prefix":"10.1128","volume":"198","author":[{"given":"Ana","family":"Antunes","sequence":"first","affiliation":[{"name":"GSK Vaccines s.r.l., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Golfieri","sequence":"additional","affiliation":[{"name":"GSK Vaccines s.r.l., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ferlicca","sequence":"additional","affiliation":[{"name":"GSK Vaccines s.r.l., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia M.","family":"Giuliani","sequence":"additional","affiliation":[{"name":"GSK Vaccines s.r.l., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Scarlato","sequence":"additional","affiliation":[{"name":"Universit\u00e0 di Bologna, Dipartimento di Farmacia e Biotecnologie, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Delany","sequence":"additional","affiliation":[{"name":"GSK Vaccines s.r.l., Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-346-2_1"},{"key":"e_1_3_3_3_2","first-page":"237","article-title":"Meningococcal disease: changes in epidemiology and prevention","volume":"4","author":"Chang Q","year":"2012","unstructured":"Chang Q, Tzeng YL, Stephens DS. 2012. 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