Trimethoprim induces heat shock proteins and protein aggregation in E. coli cells.
Trimethoprim (TMP), an inhibitor of dihydrofolate reductase, decreases the level of tetrahydrofolate supplying one-carbon units for biosynthesis of nucleotides, proteins, and panthotenate. We have demonstrated for the first time that one of the effects of the TMP action in E. coli cells is protein aggregation and induction of heat shock proteins (Hsps). TMP caused induction of DnaK, DnaJ, GroEL, ClpB, and IbpA/B Hsps. Among these Hsps, IbpA/B were most efficiently induced by TMP and coaggregated with the insoluble proteins. Upon folate stress, deletion of the delta ibpA/B operon resulted in increased protein aggregation but did not influence cell viability.
Laskowska
Ewa
E
Department of Biochemistry, University of Gdańsk, Kładki 24, 80-822 Gdańsk, Poland. lasko@biotech.univ.gda.pl
Kuczyńska-Wiśnik
Dorota
D
Bak
Monika
M
Lipińska
Barbara
B
D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000494:pharmacology; D017353:Gene Deletion; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014295:Trimethoprim / Q000494:pharmacology*
D029968:Escherichia coli Proteins; D005493:Folic Acid Antagonists; D006360:Heat-Shock Proteins; C097578:IbpA protein, E coli; C097579:IbpB protein, E coli; D014295:Trimethoprim