The Effect of Pharmacological Agents on the Expression of the Genes of the Chaperone GrpE and Co-Chaperone IbpA in Cells

To study the effect of pharmacological agents on the expression of the DnaK chaperone and IbpA co-chaperone genes, two biosensors were used: MG1655 pGrpE-lux and MG1655 pIbpA-lux. The operon of the bacterium , substituted for the promoters of the and the genes correspondingly, serves as a reporter for the expression of these genes. The induction of the expression of the and genes indicates the ability of the tested compounds to influence protein folding and refolding. 10 of the 12 tested compounds are known pharmacological agents. The fluoroquinoline topoisomerase inhibitors — the antibiotics ciprofloxacin and nalidixic acid, the cytostatics 5-fluorouracil and mitomycin C, as well as the antibacterial agent dioxin — elicited a response in both biosensors, indicating the ability of these substances to influence the structure of both synthesized proteins and proteins functioning in the cell. Rifampicin induced a response only in the pGrpE-lux biosensor, whereas cisplatin and 5-bromo-2-deoxyuridine induced a response only in the pIbpA-lux biosensor. The cytostatic actinomycin D showed high toxicity to bacteria, which did not allow its activity against chaperones to be registered. 6-Thioguanine did not elicit a response from both biosensors. All these compounds have mutagenic/genotoxic activity. The standard genotoxicants/mutagens 4-NQO and NaN induced a response in both biosensors.