title: Transcriptional profiling of Neisseria meningitidis interacting with human epithelial cells in a long-term in vitro colonization model.
abstract: Neisseria meningitidis is a commensal of humans that can colonize the nasopharyngeal epithelium for weeks to months and occasionally invades to cause life-threatening septicemia and meningitis. Comparatively little is known about meningococcal gene expression during colonization beyond those first few hours. In this study, the transcriptome of adherent serogroup B N. meningitidis strain MC58 was determined at intervals during prolonged cocultivation with confluent monolayers of the human respiratory epithelial cell line 16HBE14. At different time points up to 21 days, 7 to 14% of the meningococcal genome was found to be differentially regulated. The transcriptome of adherent meningococci obtained after 4 h of coculture was markedly different from that obtained after prolonged cocultivation (24 h, 96 h, and 21 days). Genes persistently upregulated during prolonged cocultivation included three genes (hfq, misR/phoP, and lrp) encoding global regulatory proteins. Many genes encoding known adhesins involved in epithelial adherence were upregulated, including those of a novel locus (spanning NMB0342 to NMB0348 [NMB0342-NMB0348]) encoding epithelial cell-adhesive function. Sixteen genes (including porA, porB, rmpM, and fbpA) encoding proteins previously identified by their immunoreactivity to sera from individuals colonized long term with serogroup B meningococci were also upregulated during prolonged cocultivation, indicating that our system models growth conditions in vivo during the commensal state. Surface-expressed proteins downregulated in the nasopharynx (and thus less subject to selection pressure) but upregulated in the bloodstream (and thus vulnerable to antibody-mediated bactericidal activity) should be interesting candidate vaccine antigens, and in this study, three new proteins fulfilling these criteria have been identified: NMB0497, NMB0866, and NMB1882.
authors: Section of Paediatrics, Department of Medicine, Imperial College London, St. Mary's Campus, London, United Kingdom.
authors: Ariann
authors: A
authors: Hey
authors: Ming-Shi
authors: MS
authors: Li
authors: Michael J
authors: MJ
authors: Hudson
authors: Paul R
authors: PR
authors: Langford
authors: J Simon
authors: JS
authors: Kroll
mesh_terms: D001422:Bacterial Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D005798:Genes, Bacterial; D006801:Humans; D008137:Longitudinal Studies; D009345:Neisseria meningitidis / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D013997:Time Factors; D059467:Transcriptome; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D037521:Virulence Factors
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