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

To study the effect of pharmacological agents on the expression of the DnaK chaperone and IbpA co-chaperone genes, two biosensors were used: Escherichia coli MG1655 pGrpE-lux and MG1655 pIbpA-lux. The luxCDABE operon of the bacterium P. luminescens, substituted for the promoters of the grpE and the ibpA genes respectively, serves as a reporter for the expression of these genes. The induction of the expression of the grpE and ibpA genes indicates the ability of the tested compounds to influence protein folding and refolding. Ten of the 12 tested compounds are known pharmacological agents. The fluoroquinolone topoisomerase inhibitors—the antibiotics ciprofloxacin and nalidixic acid, the cytostatics 5-fluorouracil and mitomycin C, and the antibacterial agent dioxidin—elicited a response in both biosensors, indicating the ability of these substances to influence the structure of both de novo 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 either of the biosensors. All these compounds have mutagenic/genotoxic activity. The standard genotoxicants/mutagens 4-NQO and NaN3 induced a response in both biosensors.