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Multilayer regulation of Neisseria meningitidis NHBA at physiologically relevant temperatures

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Borghi_2022_Microorganisms_ultilayer_regulation_Neisseria_meningitidis_NHBA_CC.pdf (2.198Mb)
Date
18/04/2022
Author
Borghi, Sara
Antunes, Ana
Haag, Andreas F.
Spinsanti, Marco
Brignoli, Tarcisio
Ndoni, Enea
Scarlato, Vincenzo
Delany, Isabel
Keywords
Vaccine
Neisseria meningitidis
NHBA
Thermoregulation
4CmenB
QR180 Immunology
NDAS
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Abstract
Neisseria 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.
Citation
Borghi , 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/microorganisms10040834
Publication
Microorganisms
Status
Peer reviewed
DOI
https://doi.org/10.3390/microorganisms10040834
ISSN
2076-2607
Type
Journal article
Rights
Copyright: © 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/).
Description
This research was sponsored by GlaxoSmithKline Biologicals SA. A.F.H. was funded by Marie Sklodowska-Curie Intra-European Fellowships (PIEF-GA-2012-328377).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/25365

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