title: Control of lipopolysaccharide biosynthesis by FtsH-mediated proteolysis of LpxC is conserved in enterobacteria but not in all gram-negative bacteria.
abstract: Despite the essential function of lipopolysaccharides (LPS) in Gram-negative bacteria, it is largely unknown how the exact amount of this molecule in the outer membrane is controlled. The first committed step in LPS biosynthesis is catalyzed by the LpxC enzyme. In Escherichia coli, the cellular concentration of LpxC is adjusted by the only essential protease in this organism, the membrane-anchored metalloprotease FtsH. Turnover of E. coli LpxC requires a length- and sequence-specific C-terminal degradation signal. LpxC proteins from Salmonella, Yersinia, and Vibrio species carry similar C-terminal ends and, like the E. coli enzyme, were degraded by FtsH. Although LpxC proteins are highly conserved in Gram-negative bacteria, there are striking differences in their C termini. The Aquifex aeolicus enzyme, which is devoid of the C-terminal extension, was stable in E. coli, whereas LpxC from the alphaproteobacteria Agrobacterium tumefaciens and Rhodobacter capsulatus was degraded by the Lon protease. Proteolysis of the A. tumefaciens protein required the C-terminal end of LpxC. High stability of Pseudomonas aeruginosa LpxC in E. coli and P. aeruginosa suggested that Pseudomonas uses a proteolysis-independent strategy to control its LPS content. The differences in LpxC turnover along with previously reported differences in susceptibility against antimicrobial compounds have important implications for the potential of LpxC as a drug target.
authors.affiliation: Lehrstuhl für Biologie der Mikroorganismen, Ruhr-Universität Bochum, Bochum, Germany.
authors.forename: Sina
authors.initials: S
authors.lastname: Langklotz
authors.forename: Michael
authors.initials: M
authors.lastname: Schäkermann
authors.forename: Franz
authors.initials: F
authors.lastname: Narberhaus
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008070:Lipopolysaccharides