Mutations in three distinct loci cause resistance to peptide deformylase inhibitors in Bacillus subtilis.
Bacillus subtilis mutants with resistance against peptide deformylase inhibitors were isolated. All showed a bypass of the pathway through mutations in three genes required for formylation of Met-tRNA(fMet), fmt, folD, and glyA. glyA corresponds to a yet uncharacterized locus inducing resistance. The bypass of formylation caused robust fitness reduction but was not accompanied by alterations of the transcription profile. A subtle adaptation of the enzymes of the intermediary metabolism was observed.
Duroc
Yann
Y
Protein Maturation, Cell Fate and Therapeutics, ISV, UPR2355, Centre National de la Recherche Scientifique, Gif-sur-Yvette Cedex, France.
Giglione
Carmela
C
Meinnel
Thierry
T
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics; D006877:Hydroxamic Acids / Q000494:pharmacology; D045064:Methenyltetrahydrofolate Cyclohydrolase / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D012358:RNA, Transfer, Met / Q000235:genetics
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D012358:RNA, Transfer, Met; C089238:fMet-tRNA(fMet); D012696:Glycine Hydroxymethyltransferase; D000581:Amidohydrolases; C084507:peptide deformylase; D045064:Methenyltetrahydrofolate Cyclohydrolase; C010531:actinonin