title: Inactivation ofNMB0419, Encoding a Sel1-Like Repeat (SLR) Protein, in Neisseria meningitidis Is Associated with Differential Expression of Genes Belonging to the Fur Regulon and Reduced Intraepithelial Replication.
abstract: Neisseria meningitidisis a commensal microbe that colonizes the human nasopharynx but occasionally invades the bloodstream to cause life-threatening infection.N. meningitidisMC58NMB0419encodes a Sel1-like repeat (SLR)-containing protein, previously implicated in invasion of epithelial cells. A gene-regulatory function was revealed inEscherichia coliexpressing plasmid-borneNMB0419and showing significantly increased epithelial adherence compared to the wild type, due to increased expression of mannose-sensitive type 1 pili. While a meningococcalNMB0419mutant did not have altered epithelial adherence, in a transcriptome-wide comparison of the wild type and anNMB0419mutant, a large proportion of genes differentially regulated in the mutant were involved in iron acquisition and metabolism. Fifty-one percent and 38% of genes, respectively, up- and downregulated in theNMB0419mutant had previously been identified as being induced and repressed by meningococcal Fur. Anin vitrogrowth defect of theNMB0419mutant under iron restriction was consistent with the downregulation oftbpABandhmbR, while an intraepithelial replication defect was consistent with the downregulation oftonB,exbB, andexbD, based on a known phenotype of a meningococcaltonBmutant. Disruption of the N-terminal NMB0419 signal peptide, predicted to export the protein beyond the cytoplasmic membrane, resulted in loss of functional traits inN. meningitidisandE. coliOur study indicates that the expression ofNMB0419is associated with transcriptional changes counterbalancing the regulatory function of Fur, offering a new perspective on regulatory mechanisms involved in meningococcal interaction with epithelial cells, and suggests new insights into the roles of SLR-containing genes in other bacteria.
authors.affiliation: Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Li
authors.affiliation: Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom p.langford@imperial.ac.uk s.kroll@imperial.ac.uk.
authors.forename: Paul R
authors.identifier: http://orcid.org/0000-0002-6368-4724
authors.initials: PR
authors.lastname: Langford
authors.affiliation: Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom p.langford@imperial.ac.uk s.kroll@imperial.ac.uk.
authors.forename: J Simon
authors.initials: JS
authors.lastname: Kroll
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D007501:Iron / Q000378:metabolism; D009345:Neisseria meningitidis / Q000235:genetics* / Q000254:growth & development*; D010957:Plasmids; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018085:Regulon; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron
keywords: Fur regulon; NMB0419; Neisseria meningitidis; Sel1-like repeat; epithelial cells; intracellular replication; iron acquisition; transcriptome