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Comprehensive identification of meningococcal genes and small noncoding RNAs required for host cell colonization

dc.contributor.authorCapel, Elena
dc.contributor.authorZomer, Aldert L.
dc.contributor.authorNussbaumer, Thomas
dc.contributor.authorBole, Christine
dc.contributor.authorIzac, Brigitte
dc.contributor.authorFrapy, Eric
dc.contributor.authorMeyer, Julie
dc.contributor.authorBouzinba-Ségard, Haniaa
dc.contributor.authorBille, Emmanuelle
dc.contributor.authorJamet, Anne
dc.contributor.authorCavau, Anne
dc.contributor.authorLetourneur, Franck
dc.contributor.authorBourdoulous, Sandrine
dc.contributor.authorRattei, Thomas
dc.contributor.authorNassif, Xavier
dc.contributor.authorCoureuil, Mathieu
dc.contributor.authorSeifert, H.
dc.contributor.authorShafer, William
dc.date.accessioned2022-06-14T15:26:39Z
dc.date.available2022-06-14T15:26:39Z
dc.date.issued2016
dc.description© 2016 Capel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.pt_PT
dc.description.abstractNeisseria meningitidis is a leading cause of bacterial meningitis and septicemia, affecting infants and adults worldwide. N. meningitidis is also a common inhabitant of the human nasopharynx and, as such, is highly adapted to its niche. During bacteremia, N. meningitidis gains access to the blood compartment, where it adheres to endothelial cells of blood vessels and causes dramatic vascular damage. Colonization of the nasopharyngeal niche and communication with the different human cell types is a major issue of the N. meningitidis life cycle that is poorly understood. Here, highly saturated random transposon insertion libraries of N. meningitidis were engineered, and the fitness of mutations during routine growth and that of colonization of endothelial and epithelial cells in a flow device were assessed in a transposon insertion site sequencing (Tn-seq) analysis. This allowed the identification of genes essential for bacterial growth and genes specifically required for host cell colonization. In addition, after having identified the small noncoding RNAs (sRNAs) located in intergenic regions, the phenotypes associated with mutations in those sRNAs were defined. A total of 383 genes and 8 intergenic regions containing sRNA candidates were identified to be essential for growth, while 288 genes and 33 intergenic regions containing sRNA candidates were found to be specifically required for host cell colonization. Importance: Meningococcal meningitis is a common cause of meningitis in infants and adults. Neisseria meningitidis (meningococcus) is also a commensal bacterium of the nasopharynx and is carried by 3 to 30% of healthy humans. Under some unknown circumstances, N. meningitidis is able to invade the bloodstream and cause either meningitis or a fatal septicemia known as purpura fulminans. The onset of symptoms is sudden, and death can follow within hours. Although many meningococcal virulence factors have been identified, the mechanisms that allow the bacterium to switch from the commensal to pathogen state remain unknown. Therefore, we used a Tn-seq strategy coupled to high-throughput DNA sequencing technologies to find genes for proteins used by N. meningitidis to specifically colonize epithelial cells and primary brain endothelial cells. We identified 383 genes and 8 intergenic regions containing sRNAs essential for growth and 288 genes and 33 intergenic regions containing sRNAs required specifically for host cell colonization.pt_PT
dc.description.sponsorshipThis work was supported by ANR grant ANR-14-IFEC-0006-01 call ERANET INFECT-ERA 2014, the grant program EMERGENCE from La Mairie de Paris, and a postdoctoral grant supported by the DIM Malinf from the Conseil Régional de l’Ile-De-France. The laboratory of X.N. is supported by INSERM, CNRS, Université Paris Descartes, and the Fondation pour la Recherche Médicale.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationmBio. 2016 Aug 2;7(4):e01173-16pt_PT
dc.identifier.doi10.1128/mBio.01173-16pt_PT
dc.identifier.eissn2150-7511
dc.identifier.issn2161-2129
dc.identifier.urihttp://hdl.handle.net/10451/53378
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherASM Journalspt_PT
dc.relation.publisherversionhttps://journals.asm.org/journal/mbiopt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleComprehensive identification of meningococcal genes and small noncoding RNAs required for host cell colonizationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue4pt_PT
oaire.citation.titlemBiopt_PT
oaire.citation.volume7pt_PT
person.familyNameJamet
person.givenNameAnne
person.identifier.orcid0000-0002-1902-6943
person.identifier.ridE-1288-2014
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication0709933c-03f9-4dda-ba18-6117de50bd62
relation.isAuthorOfPublication.latestForDiscovery0709933c-03f9-4dda-ba18-6117de50bd62

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