Premium
Strategies towards a better understanding of antibiotic action: Folate pathway inhibition in Haemophilus influenzae as an example
Author(s) -
Evers Stefan,
Padova Karin Di,
Meyer Michelle,
Fountoulakis Michael,
Keck Wolfgang,
Gray Christopher P.
Publication year - 1998
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.1150191116
Subject(s) - groes , groel , biochemistry , haemophilus influenzae , methionine , amino acid , serine , escherichia coli , sulfamethoxazole , trimethoprim , protein biosynthesis , biology , glycine , threonine , enzyme , chemistry , antibiotics , gene
Two‐dimensional electrophoresis was applied to the global analysis of the cellular response of Haemophilus influenzae to sulfamethoxazole and trimethoprim, both inhibitors of tetrahydrofolate synthesis. Deregulation of the synthesis rate of 118 proteins, involved in different metabolic pathways, was observed. The regulation of the genes involved in the metabolism of the amino acids methionine, threonine, serine, glycine, and aspartate was investigated in detail by analysis of protein synthesis and Northern hybridization. The results suggested that the synthesis of methionine biosynthetic enzymes in H. influenzae is regulated in a similar fashion as in Escherichia coli. A good correlation between the results obtained by Northern hybridization and quantification of protein synthesis was observed. In contrast to trimethoprim, sulfamethoxazole triggered the increased synthesis of the heat shock proteins DnaK, GroEL, and GroES.