title: Identification of novel essential Escherichia coli genes conserved among pathogenic bacteria.
abstract: We deleted a subset of 27 open reading frames (ORFs) from Escherichia coli which encode previously uncharacterized, probably soluble gene products homologous to proteins from a broad spectrum of bacterial pathogens such as Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis and only distantly related to eukaryotic proteins. Six novel bacteria-specific genes essential for growth in complex medium could be identified through a combination of bioinformatics-based and experimental approaches. We also compared our data to published results of gene inactivation projects with Mycoplasma genitalium and Bacillus subtilis and looked for homologs in all known prokaryotic genomes. Such analyses highlight the enormous metabolic flexibility of prokaryotes. Six of 27 studied genes have been functionally characterized up to now, amongst these four of the essential genes. The gene products YgbP, YgbB and YchB are involved in the non-mevalonate pathway of isoprenoid biosynthesis. KdtB is characterized as the posphopantetheine adenylyltransferase CoaD. There are indications that the other two essential gene products YjeE and YqgF, which we have identified, also possess enzymatic functions. These findings demonstrate the potential of such proteins to be used in screening of large chemical libraries for inhibitors which could be further developed to novel broad-spectrum antibiotics.
authors.affiliation: Institute for Anti-infectives Research, Pharma Research, Bayer AG, Wuppertal, Germany. Christoph.Freiberg.CF@bayer-ag.de
authors.forename: C
authors.initials: C
authors.lastname: Freiberg
authors.forename: B
authors.initials: B
authors.lastname: Wieland
authors.forename: F
authors.initials: F
authors.lastname: Spaltmann
authors.forename: K
authors.initials: K
authors.lastname: Ehlert
authors.forename: H
authors.initials: H
authors.lastname: Brötz
authors.forename: H
authors.initials: H
authors.lastname: Labischinski
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000235:genetics; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics; D013293:Enterococcus faecalis / Q000235:genetics* / Q000472:pathogenicity; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D020043:Genes, Essential; D006193:Haemophilus influenzae / Q000235:genetics* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D009174:Mycoplasma / Q000235:genetics / Q000472:pathogenicity; D009713:Nucleotidyltransferases / Q000235:genetics; D016366:Open Reading Frames; D019761:Phosphorus-Oxygen Lyases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D010957:Plasmids; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C404502:IspE protein, E coli; C400183:4-diphosphocytidyl-2-C--methylerythritol synthase; D009713:Nucleotidyltransferases; D019761:Phosphorus-Oxygen Lyases; C400181:ISPF protein, E coli