气候变化领域集成服务门户(CCPortal): The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus

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DOI	10.1073/pnas.2109364118
	The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus
	Barnier J.-P.; Meyer J.; Kolappan S.; Bouzinbaegard H.; Gesbert G.; Jamet A.; Frapy E.; Schonherr-Hellec S.; Capel E.; Virion Z.; Dupuis M.; Bille E.; Morand P.; Schmitt T.; Bourdoulous S.; Nassif X.; Craig L.; Coureuil M.; Craig L.; Coureuil M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:45
英文摘要	Neisseria meningitidis utilizes type IV pili (T4P) to adhere to and colonize host endothelial cells, a process at the heart of meningococcal invasive diseases leading to meningitis and sepsis. T4P are polymers of an antigenically variable major pilin building block, PilE, plus several core minor pilins that initiate pilus assembly and are thought to be located at the pilus tip. Adhesion of N. meningitidis to human endothelial cells requires both PilE and a conserved noncore minor pilin PilV, but the localization of PilV and its precise role in this process remains to be clarified. Here, we show that both PilE and PilV promote adhesion to endothelial vessels in vivo. The substantial adhesion defect observed for pilV mutants suggests it is the main adhesin. Consistent with this observation, superresolution microscopy showed the abundant distribution of PilV throughout the pilus. We determined the crystal structure of PilV and modeled it within the pilus filament. The small size of PilV causes it to be recessed relative to adjacent PilE subunits, which are dominated by a prominent hypervariable loop. Nonetheless, we identified a conserved surface-exposed adhesive loop on PilV by alanine scanning mutagenesis. Critically, antibodies directed against PilV inhibit N. meningitidis colonization of human skin grafts. These findings explain how N. meningitidis T4P undergo antigenic variation to evade the humoral immune response while maintaining their adhesive function and establish the potential of this highly conserved minor pilin as a vaccine and therapeutic target for the prevention and treatment of N. meningitidis infections. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Adhesion; Host-pathogen interaction; Neisseria meningitidis; PilV; Type IV pili
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238763
作者单位	Faculte deMedecine, Universite de Paris, Paris, 75006, France; INSERMU1151, CNRS UMR 8253, Institut Necker Enfants-Malades, Paris, 75015, France; Service de Microbiologie, Assistance Publique-Hôpitaux de Paris, Centre-Universite de Paris, Hôpital Necker Enfants-Malades, Paris, 75015, France; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A 3Y6, Canada; INSERMU1016, CNRS UMR 8104, Institut Cochin, Paris, 75014, France; Service de Bacteriologie, Assistance Publique-Hôpitaux de Paris, Centre-Universite de Paris, Hôpital Cochin, Paris, 75014, France; Service de Chirurgie Reconstructrice et Plastique, Groupe Hospitalier Paris Saint-Joseph, Paris, 75014, France
推荐引用方式 GB/T 7714	Barnier J.-P.,Meyer J.,Kolappan S.,et al. The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus[J],2021,118(45).
APA	Barnier J.-P..,Meyer J..,Kolappan S..,Bouzinbaegard H..,Gesbert G..,...&Coureuil M..(2021).The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus.Proceedings of the National Academy of Sciences of the United States of America,118(45).
MLA	Barnier J.-P.,et al."The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus".Proceedings of the National Academy of Sciences of the United States of America 118.45(2021).