title: Slam is an outer membrane protein that is required for the surface display of lipidated virulence factors in Neisseria.
abstract: Lipoproteins decorate the surface of many Gram-negative bacterial pathogens, playing essential roles in immune evasion and nutrient acquisition. In Neisseria spp., the causative agents of gonorrhoea and meningococcal meningitis, surface lipoproteins (SLPs) are required for virulence and have been extensively studied as prime candidates for vaccine development. However, the machinery and mechanism that allow for the surface display of SLPs are not known. Here, we describe a transposon (Tn5)-based search for the proteins required to deliver SLPs to the surface of Neisseria meningitidis, revealing a family of proteins that we have named the surface lipoprotein assembly modulator (Slam). N. meningitidis contains two Slam proteins, each exhibiting distinct substrate preferences. The Slam proteins are sufficient to reconstitute SLP transport in laboratory strains of Escherichia coli, which are otherwise unable to efficiently display these lipoproteins on their cell surface. Immunoprecipitation and domain probing experiments suggest that the SLP, TbpB, interacts with Slam during the transit process; furthermore, the membrane domain of Slam is sufficient for selectivity and proper surface display of SLPs. Rather than being a Neisseria-specific factor, our bioinformatic analysis shows that Slam can be found throughout proteobacterial genomes, indicating a conserved but until now unrecognized virulence mechanism.
authors: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Yogesh
authors: Y
authors: Hooda
authors: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Christine Chieh-Lin
authors: CC
authors: Lai
authors: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Andrew
authors: A
authors: Judd
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Carolyn M
authors: CM
authors: Buckwalter
authors: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Hyejin Esther
authors: http://orcid.org/0000-0003-3537-3184
authors: HE
authors: Shin
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Scott D
authors: http://orcid.org/0000-0002-1477-3616
authors: SD
authors: Gray-Owen
authors: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Trevor F
authors: TF
authors: Moraes
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D004251:DNA Transposable Elements; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005816:Genetic Complementation Test; D005820:Genetic Testing; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004251:DNA Transposable Elements; D008074:Lipoproteins; D008565:Membrane Proteins; D037521:Virulence Factors