title: Structure of the bacterial cell division determinant GpsB and its interaction with penicillin-binding proteins.
abstract: Each bacterium has to co-ordinate its growth with division to ensure genetic stability of the population. Consequently, cell division and growth are tightly regulated phenomena, albeit different bacteria utilise one of several alternative regulatory mechanisms to maintain control. Here we consider GpsB, which is linked to cell growth and division in Gram-positive bacteria. ΔgpsB mutants of the human pathogen Listeria monocytogenes show severe lysis, division and growth defects due to distortions of cell wall biosynthesis. Consistent with this premise, GpsB interacts both in vitro and in vivo with the major bi-functional penicillin-binding protein. We solved the crystal structure of GpsB and the interaction interfaces in both proteins are identified and validated. The inactivation of gpsB results in strongly attenuated virulence in animal experiments, comparable in degree to classical listerial virulence factor mutants. Therefore, GpsB is essential for in vitro and in vivo growth of a highly virulent food-borne pathogen, suggesting that GpsB could be a target for the future design of novel antibacterials.
authors.affiliation: FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany.
authors.forename: Jeanine
authors.initials: J
authors.lastname: Rismondo
authors.affiliation: Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cleverley
authors.affiliation: Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: Harriet V
authors.initials: HV
authors.lastname: Lane
authors.affiliation: FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany.|Department of General Microbiology, Institute of Microbiology and Genetics, Georg-August University, Göttingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Großhennig
authors.affiliation: FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Steglich
authors.affiliation: ZBS 4 - Advanced Light and Electron Microscopy, Robert Koch Institute, Berlin, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Möller
authors.affiliation: Institute of Medical Microbiology, University of Gießen, Gießen, Germany.
authors.forename: Gopala Krishna
authors.initials: GK
authors.lastname: Mannala
authors.affiliation: Institute of Medical Microbiology, University of Gießen, Gießen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Hain
authors.affiliation: Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
authors.affiliation: FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Halbedel
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002473:Cell Wall / Q000378:metabolism; D008089:Listeria monocytogenes / Q000166:cytology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D046915:Penicillin-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D046915:Penicillin-Binding Proteins; D037521:Virulence Factors