{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:06:36Z","timestamp":1791273996211,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,2,11]],"date-time":"2014-02-11T00:00:00Z","timestamp":1392076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,2,28]],"date-time":"2014-02-28T00:00:00Z","timestamp":1393545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:bold>T<\/jats:bold>\n            ype IV pili (Tfp) are expressed by many Gram-negative bacteria to promote aggregation, adhesion, internalization, twitching motility, or natural transformation. Tfp of\n            <jats:named-content content-type=\"genus-species\">Neisseria meningitidis<\/jats:named-content>\n            , the causative agent of cerebrospinal meningitis, are involved in the colonization of human nasopharynx. After invasion of the bloodstream, Tfp allow adhesion of\n            <jats:named-content content-type=\"genus-species\">N. meningitidis<\/jats:named-content>\n            to human endothelial cells, which leads to the opening of the blood-brain barrier and meningitis. To achieve firm adhesion,\n            <jats:named-content content-type=\"genus-species\">N. meningitidis<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">Neisseria meningitidis<\/jats:named-content>\n            has evolved a powerful tool to adapt easily to many niches by modifying its ability to interact with host cells.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Type IV pili (Tfp) are long appendages expressed by many Gram-negative bacteria, including\n            <jats:named-content content-type=\"genus-species\">Neisseria meningitidis<\/jats:named-content>\n            , the causative agent of cerebrospinal meningitis. These pili are involved in many aspects of pathogenesis: natural competence, aggregation, adhesion, and twitching motility. More specifically,\n            <jats:named-content content-type=\"genus-species\">Neisseria meningitidis<\/jats:named-content>\n            , 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.\n          <\/jats:p>","DOI":"10.1128\/mbio.01024-13","type":"journal-article","created":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T02:34:41Z","timestamp":1392172481000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["The Hypervariable Region of Meningococcal Major Pilin PilE Controls the Host Cell Response via Antigenic Variation"],"prefix":"10.1128","volume":"5","author":[{"given":"Florence","family":"Miller","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Descartes, UMRS U1151, Sorbonne Paris Cit\u00e9, Facult\u00e9 de M\u00e9decine, Paris, France"},{"name":"Institut National de la Sante et de la recherche Medicale U1002, Paris, 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