title: A novel phase-variable autotransporter serine protease, AusI, of Neisseria meningitidis.
abstract: The sequenced genomes of pathogenic Neisseria meningitidis strains contain up to eight genes putatively encoding autotransporters, which are secreted proteins implicated in virulence. Here, we have characterized one of these genes, designated ausI, which encodes an autotransporter of the serine protease family. It was found to be specific for N. meningitidis and present in 14 out of 20 isolates, although only six of them expressed the gene. We show that expression of the gene is subject to phase variation as a result of a variable number of cytosines in a poly-C tract in the coding region. The open reading frame went out-of-phase at the poly-C tract in seven strains that did not express AusI. In the eighth strain, the open reading frame remained in frame at the poly-C tract, but it was disrupted by a premature stop codon further downstream. In accordance with its assignment as an autotransporter, a secreted AusI passenger domain was released into the extracellular milieu. This release was influenced by another autotransporter, NalP, as different forms of AusI were produced in the presence or absence of NalP. In silico sequence analysis suggested several putative functions for AusI, which, however, could not be confirmed experimentally.
authors.affiliation: Department of Molecular Microbiology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. P.vanUlsen@bio.uu.nl
authors.forename: Peter
authors.initials: P
authors.lastname: van Ulsen
authors.forename: Ben
authors.initials: B
authors.lastname: Adler
authors.forename: Peter
authors.initials: P
authors.lastname: Fassler
authors.forename: Maarten
authors.initials: M
authors.lastname: Gilbert
authors.forename: Muriel
authors.initials: M
authors.lastname: van Schilfgaarde
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Loek
authors.initials: L
authors.lastname: van Alphen
authors.forename: Jan
authors.initials: J
authors.lastname: Tommassen
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D018389:Codon, Nonsense; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D016368:Frameshift Mutation; D015870:Gene Expression; D005798:Genes, Bacterial; D026901:Membrane Transport Proteins / Q000502:physiology; D009345:Neisseria meningitidis / Q000201:enzymology*; D016366:Open Reading Frames / Q000235:genetics; D011066:Poly C / Q000235:genetics; D016133:Polymerase Chain Reaction; D021381:Protein Transport / Q000502:physiology*; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D004269:DNA, Bacterial; D026901:Membrane Transport Proteins; D037521:Virulence Factors; D011066:Poly C; C480853:NalP protein, Neisseria meningitidis; D012697:Serine Endopeptidases