The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation

ABSTRACT Type IV pili (Tfp) are expressed by many Gram-negative bacteria to promote aggregation, adhesion, internalization, twitching motility, or natural transformation. Tfp of Neisseria meningitidis, the causative agent of cerebrospinal meningitis, are involved in the colonization of human nasopha...

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Autores principales:	Florence Miller, Gilles Phan, Terry Brissac, Coralie Bouchiat, Ghislaine Lioux, Xavier Nassif, Mathieu Coureuil
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/55b992170e664b94b197f36570d33931
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spelling	oai:doaj.org-article:55b992170e664b94b197f36570d339312021-11-15T15:45:11ZThe Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation10.1128/mBio.01024-132150-7511https://doaj.org/article/55b992170e664b94b197f36570d339312014-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01024-13https://doaj.org/toc/2150-7511ABSTRACT Type IV pili (Tfp) are expressed by many Gram-negative bacteria to promote aggregation, adhesion, internalization, twitching motility, or natural transformation. Tfp of Neisseria meningitidis, the causative agent of cerebrospinal meningitis, are involved in the colonization of human nasopharynx. After invasion of the bloodstream, Tfp allow adhesion of N. meningitidis to human endothelial cells, which leads to the opening of the blood-brain barrier and meningitis. To achieve firm adhesion, N. meningitidis induces a host cell response that results in elongation of microvilli surrounding the meningococcal colony. Here we study the role of the major pilin subunit PilE during host cell response using human dermal microvascular endothelial cells and the pharynx carcinoma-derived FaDu epithelial cell line. We first show that some PilE variants are unable to induce a host cell response. By engineering PilE mutants, we observed that the PilE C-terminus domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and that hypervariable regions confer different host cell specificities. Moreover, the study of point mutants of the pilin D-region combined with structural modeling of PilE revealed that the D-region contains two independent regions involved in signaling to human dermal microvascular endothelial cells (HDMECs) or FaDu cells. Our results indicate that the diversity of the PilE D-region sequence allows the induction of the host cell response via several receptors. This suggests that Neisseria meningitidis has evolved a powerful tool to adapt easily to many niches by modifying its ability to interact with host cells. IMPORTANCE Type IV pili (Tfp) are long appendages expressed by many Gram-negative bacteria, including Neisseria meningitidis, the causative agent of cerebrospinal meningitis. These pili are involved in many aspects of pathogenesis: natural competence, aggregation, adhesion, and twitching motility. More specifically, Neisseria meningitidis, which is devoid of a secretion system to manipulate its host, has evolved its Tfp to signal to brain endothelial cells and open the blood-brain barrier. In this report, we investigate, at the molecular level, the involvement of the major pilin subunit PilE in host cell response. Our results indicate that the PilE C-terminal domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and contains two independent regions involved in host cell signaling.Florence MillerGilles PhanTerry BrissacCoralie BouchiatGhislaine LiouxXavier NassifMathieu CoureuilAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 1 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Florence Miller Gilles Phan Terry Brissac Coralie Bouchiat Ghislaine Lioux Xavier Nassif Mathieu Coureuil The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation
description	ABSTRACT Type IV pili (Tfp) are expressed by many Gram-negative bacteria to promote aggregation, adhesion, internalization, twitching motility, or natural transformation. Tfp of Neisseria meningitidis, the causative agent of cerebrospinal meningitis, are involved in the colonization of human nasopharynx. After invasion of the bloodstream, Tfp allow adhesion of N. meningitidis to human endothelial cells, which leads to the opening of the blood-brain barrier and meningitis. To achieve firm adhesion, N. meningitidis induces a host cell response that results in elongation of microvilli surrounding the meningococcal colony. Here we study the role of the major pilin subunit PilE during host cell response using human dermal microvascular endothelial cells and the pharynx carcinoma-derived FaDu epithelial cell line. We first show that some PilE variants are unable to induce a host cell response. By engineering PilE mutants, we observed that the PilE C-terminus domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and that hypervariable regions confer different host cell specificities. Moreover, the study of point mutants of the pilin D-region combined with structural modeling of PilE revealed that the D-region contains two independent regions involved in signaling to human dermal microvascular endothelial cells (HDMECs) or FaDu cells. Our results indicate that the diversity of the PilE D-region sequence allows the induction of the host cell response via several receptors. This suggests that Neisseria meningitidis has evolved a powerful tool to adapt easily to many niches by modifying its ability to interact with host cells. IMPORTANCE Type IV pili (Tfp) are long appendages expressed by many Gram-negative bacteria, including Neisseria meningitidis, the causative agent of cerebrospinal meningitis. These pili are involved in many aspects of pathogenesis: natural competence, aggregation, adhesion, and twitching motility. More specifically, Neisseria meningitidis, which is devoid of a secretion system to manipulate its host, has evolved its Tfp to signal to brain endothelial cells and open the blood-brain barrier. In this report, we investigate, at the molecular level, the involvement of the major pilin subunit PilE in host cell response. Our results indicate that the PilE C-terminal domain, which contains a disulfide bonded region (D-region), is critical for the host cell response and contains two independent regions involved in host cell signaling.
format	article
author	Florence Miller Gilles Phan Terry Brissac Coralie Bouchiat Ghislaine Lioux Xavier Nassif Mathieu Coureuil
author_facet	Florence Miller Gilles Phan Terry Brissac Coralie Bouchiat Ghislaine Lioux Xavier Nassif Mathieu Coureuil
author_sort	Florence Miller
title	The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation
title_short	The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation
title_full	The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation
title_fullStr	The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation
title_full_unstemmed	The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation
title_sort	hypervariable region of meningococcal major pilin pile controls the host cell response via antigenic variation
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/55b992170e664b94b197f36570d33931
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The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation

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