title: Escherichia coli requires the protease activity of FtsH for growth.
abstract: FtsH protease, the product of the essential ftsH gene, is a membrane-bound ATP-dependent metalloprotease of Escherichia coli that has been shown to be involved in the rapid turnover of key proteins, secretion of proteins into and through the membrane, and mRNA decay. The pleiotropic effects of ftsH mutants have led to the suggestion that FtsH possesses an ATP-dependent chaperone function that is independent of its protease function. When considering FtsH as a target for novel antibacterials, it is necessary to determine which of these functions is critical for the growth and survival of bacteria. To address this, we constructed the FtsH mutants E418Q, which retains significant ATPaseactivity but lacks protease activity, and K201N, which lacks both protease and ATPase activities. These mutants were introduced into an E. coli ftsH knockout strain which has wild-type FtsH supplied from a plasmid under control of the inducible araBAD promoter. Since neither mutant would complement the ftsH defect produced in the absence of arabinose, we conclude that the protease function of FtsH is required for bacterial growth.
authors.affiliation: Department of Biochemistry, Department of Infectious Diseases, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Jayasekera
authors.forename: S K
authors.initials: SK
authors.lastname: Foltin
authors.forename: E R
authors.initials: ER
authors.lastname: Olson
authors.forename: T P
authors.initials: TP
authors.lastname: Holler
mesh_terms: D049069:ATP-Dependent Proteases; D000255:Adenosine Triphosphate / Q000378:metabolism; D001089:Arabinose / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000201:enzymology* / Q000502:physiology*; D029968:Escherichia coli Proteins; D005816:Genetic Complementation Test; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; D000255:Adenosine Triphosphate; D001089:Arabinose; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli; D008666:Metalloendopeptidases