title: Identification of an outer membrane protein required for the transport of lipopolysaccharide to the bacterial cell surface.
abstract: Lipopolysaccharide (LPS), also known as endotoxin due to its severe pathophysiological effects in infected subjects, is an essential component of the outer membrane (OM) of most Gram-negative bacteria. LPS is synthesized in the bacterial inner membrane, a process that is now well understood. In contrast, the mechanism of its transport to the outer leaflet of the OM has remained enigmatic. We demonstrate here that the OM protein, known as increased membrane permeability (Imp) or organic solvent tolerance protein, is involved in this process. An Imp-deficient mutant of Neisseria meningitidis was viable and produced severely reduced amounts of LPS. The limited amount of LPS that was still produced was not accessible to LPS-modifying enzymes expressed in the OM or added to the extracellular medium. We conclude therefore that Imp mediates the transport of LPS to the cell surface. The role of Imp in LPS biogenesis and its high conservation among Gram-negative bacteria make it an excellent target for the development of novel antibacterial compounds.
authors.affiliation: Department of Molecular Microbiology and Institute of Biomembranes, Utrecht University, 3584 CH, Utrecht, The Netherlands. m.p.bos@bio.uu.nl
authors.forename: Martine P
authors.initials: MP
authors.lastname: Bos
authors.forename: Boris
authors.initials: B
authors.lastname: Tefsen
authors.forename: Jeroen
authors.initials: J
authors.lastname: Geurtsen
authors.forename: Jan
authors.initials: J
authors.lastname: Tommassen
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism*; D017353:Gene Deletion; D007700:Kinetics; D008070:Lipopolysaccharides / Q000493:pharmacokinetics*; D016296:Mutagenesis; D009345:Neisseria meningitidis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D010957:Plasmids
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides; D009439:Neuraminidase