Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization.

Autor:	Capel E; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France., Zomer AL; Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Nussbaumer T; CUBE Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Bole C; Plateforme Génomique de l'Institut Imagine, Hôpital Necker, Paris, France., Izac B; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France INSERM U1016, Institut Cochin, CNRS UMR8104, Paris, France., Frapy E; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France., Meyer J; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France., Bouzinba-Ségard H; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France INSERM U1016, Institut Cochin, CNRS UMR8104, Paris, France., Bille E; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France., Jamet A; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France Unidade de Microbiologia Molecular e Infecção, Instituto de Medicina Molecular, Lisbon, Portugal Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France., Cavau A; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France., Letourneur F; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France INSERM U1016, Institut Cochin, CNRS UMR8104, Paris, France., Bourdoulous S; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France INSERM U1016, Institut Cochin, CNRS UMR8104, Paris, France., Rattei T; CUBE Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria., Nassif X; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France xavier.nassif@inserm.fr., Coureuil M; Institut Necker Enfants-Malades, INSERM U1151, Equipe 11, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2016 Aug 02; Vol. 7 (4). Date of Electronic Publication: 2016 Aug 02.
DOI:	10.1128/mBio.01173-16
Abstrakt:	Unlabelled: Neisseria 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. (Copyright © 2016 Capel et al.)
Databáze:	MEDLINE
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