title: Resistance of Streptococcus pneumoniae to deformylase inhibitors is due to mutations in defB.
abstract: Resistance to peptide deformylase inhibitors in Escherichia coli or Staphylococcus aureus is due to inactivation of transformylase activity. Knockout experiments in Streptococcus pneumoniae R6x indicate that the transformylase (fmt) and deformylase (defB) genes are essential and that a def paralog (defA) is not. Actinonin-resistant mutants of S. pneumoniae ATCC 49619 harbor mutations in defB but not in fmt. Reintroduction of the mutated defB gene into wild-type S. pneumoniae R6x recreates the resistance phenotype. The altered enzyme displays decreased sensitivity to actinonin.
authors.affiliation: Versicor, Inc., Fremont, California 94555, USA.
authors.forename: P
authors.initials: P
authors.lastname: Margolis
authors.forename: C
authors.initials: C
authors.lastname: Hackbarth
authors.forename: S
authors.initials: S
authors.lastname: Lopez
authors.forename: M
authors.initials: M
authors.lastname: Maniar
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Yuan
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: J
authors.initials: J
authors.lastname: Trias
mesh_terms: D000581:Amidohydrolases; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase; C010531:actinonin