title: Polar localization of the autotransporter family of large bacterial virulence proteins.
abstract: Autotransporters are an extensive family of large secreted virulence-associated proteins of gram-negative bacteria. Secretion of such large proteins poses unique challenges to bacteria. We demonstrate that autotransporters from a wide variety of rod-shaped pathogens, including IcsA and SepA of Shigella flexneri, AIDA-I of diffusely adherent Escherichia coli, and BrkA of Bordetella pertussis, are localized to the bacterial pole. The restriction of autotransporters to the pole is dependent on the presence of a complete lipopolysaccharide (LPS), consistent with known effects of LPS composition on membrane fluidity. Newly synthesized and secreted BrkA is polar even in the presence of truncated LPS, and all autotransporters examined are polar in the cytoplasm prior to secretion. Together, these findings are consistent with autotransporter secretion occurring at the poles of rod-shaped gram-negative organisms. Moreover, NalP, an autotransporter of spherically shaped Neisseria meningitidis contains the molecular information to localize to the pole of Escherichia coli. In N. meningitidis, NalP is secreted at distinct sites around the cell. These data are consistent with a model in which the secretion of large autotransporters occurs via specific conserved pathways located at the poles of rod-shaped bacteria, with profound implications for the underlying physiology of the bacterial cell and the nature of bacterial pathogen-host interactions.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, 65 Landsdowne St., Cambridge, MA 02139, USA.
authors.forename: Sumita
authors.initials: S
authors.lastname: Jain
authors.forename: Peter
authors.initials: P
authors.lastname: van Ulsen
authors.forename: Inga
authors.initials: I
authors.lastname: Benz
authors.forename: M Alexander
authors.initials: MA
authors.lastname: Schmidt
authors.forename: Rachel
authors.initials: R
authors.lastname: Fernandez
authors.forename: Jan
authors.initials: J
authors.lastname: Tommassen
authors.forename: Marcia B
authors.initials: MB
authors.lastname: Goldberg
mesh_terms: D018830:Adhesins, Escherichia coli / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001886:Bordetella pertussis / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D026901:Membrane Transport Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D012763:Shigella flexneri / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C075559:AIDA-I protein, E coli; D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C090007:BrkA protein, Bordetella pertussis; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; C096725:SepA protein, Shigella; D014157:Transcription Factors; C058483:virG protein, Shigella flexneri; C480853:NalP protein, Neisseria meningitidis; D012697:Serine Endopeptidases