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dc.contributor.authorBorghi, Sara
dc.contributor.authorAntunes, Ana
dc.contributor.authorHaag, Andreas F.
dc.contributor.authorSpinsanti, Marco
dc.contributor.authorBrignoli, Tarcisio
dc.contributor.authorNdoni, Enea
dc.contributor.authorScarlato, Vincenzo
dc.contributor.authorDelany, Isabel
dc.date.accessioned2022-05-13T11:30:11Z
dc.date.available2022-05-13T11:30:11Z
dc.date.issued2022-04-18
dc.identifier.citationBorghi , S , Antunes , A , Haag , A F , Spinsanti , M , Brignoli , T , Ndoni , E , Scarlato , V & Delany , I 2022 , ' Multilayer regulation of Neisseria meningitidis NHBA at physiologically relevant temperatures ' , Microorganisms , vol. 10 , no. 4 , 834 . https://doi.org/10.3390/microorganisms10040834en
dc.identifier.issn2076-2607
dc.identifier.otherPURE: 279050955
dc.identifier.otherPURE UUID: 6b46f252-e8c3-4af4-b580-061fd076e679
dc.identifier.otherBibtex: microorganisms10040834
dc.identifier.otherORCID: /0000-0002-6783-0231/work/111976193
dc.identifier.otherScopus: 85128450199
dc.identifier.otherWOS: 000786905000001
dc.identifier.urihttp://hdl.handle.net/10023/25365
dc.descriptionThis research was sponsored by GlaxoSmithKline Biologicals SA. A.F.H. was funded by Marie Sklodowska-Curie Intra-European Fellowships (PIEF-GA-2012-328377).en
dc.description.abstractNeisseria meningitidis colonizes the nasopharynx of humans, and pathogenic strains can disseminate into the bloodstream, causing septicemia and meningitis. NHBA is a surface-exposed lipoprotein expressed by all N. meningitidis strains in different isoforms. Diverse roles have been reported for NHBA in heparin-mediated serum resistance, biofilm formation, and adherence to host tissues. We determined that temperature controls the expression of NHBA in all strains tested, with increased levels at 30–32 °C compared to 37 °C. Higher NHBA expression at lower temperatures was measurable both at mRNA and protein levels, resulting in higher surface exposure. Detailed molecular analysis indicated that multiple molecular mechanisms are responsible for the thermoregulated NHBA expression. The comparison of mRNA steady-state levels and half-lives at 30 °C and 37 °C demonstrated an increased mRNA stability/translatability at lower temperatures. Protein stability was also impacted, resulting in higher NHBA stability at lower temperatures. Ultimately, increased NHBA expression resulted in higher susceptibility to complement-mediated killing. We propose that NHBA regulation in response to temperature downshift might be physiologically relevant during transmission and the initial step(s) of interaction within the host nasopharynx. Together these data describe the importance of NHBA both as a virulence factor and as a vaccine antigen during neisserial colonization and invasion.
dc.format.extent16
dc.language.isoeng
dc.relation.ispartofMicroorganismsen
dc.rightsCopyright: © 2022 by the authors.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).en
dc.subjectVaccineen
dc.subjectNeisseria meningitidisen
dc.subjectNHBAen
dc.subjectThermoregulationen
dc.subject4CmenBen
dc.subjectQR180 Immunologyen
dc.subjectNDASen
dc.subject.lccQR180en
dc.titleMultilayer regulation of Neisseria meningitidis NHBA at physiologically relevant temperaturesen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.identifier.doihttps://doi.org/10.3390/microorganisms10040834
dc.description.statusPeer revieweden


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