Preliminary Investigation Of The Mechanism For Fibrauretin, Gallic Acid Increasing Susceptibility Of ESBLs-producing E. Coli To β-Lactam Antibiotics

β-lactam antibiotics were commonly used drugs in human medicine and veterinarys. These drugs play a very important role in human medicine and veterinary clinic.Because of advantages as strong bactericidal activity, low toxicity, clinical efficacy and indications widely. But due to the use of unreasonable, the problem of ESBLs-producing bacteria is getting more serious.especially it bring very big difficulties for clinical anti-infection treatment When the emergence of ESBLs-producing E.coli. By now there was no such a successful strategy to restore antibacterial activities of β-lactam antibiotics against resistant strains except β-lactamase inhibitors such as clavulanic acid, sulbactam.Combination of traditonal Chinese medicine and Western medicine can play to their respective advantages, and to be able to get the efficacy is superior to traditonal Chinese medicine or Western medicine alone. Monomers are the effective ingredients of traditional Chinese medicines, so as to further study its mechanism.Therefore, the purpose of this study is to combine with P-lactam antibiotics. To select the sensitizing agents to β-lactam antibiotics from14kind of traditional Chinese medicines monomers, and the sensitization mechanism are discussed.Objective:Selecting the monomer to increase susceptibility of ESBLs-producing E.coli to β-lactam antibiotics, and explored the sensitization mechanism of the monomer which has been selected combined with β-lactam antibiotics. And hope that with treatment resistant strain of ESBLs to provide a basis for clinic of traditional Chinese medicine combine with western medicine.Methods:1.Two-fold diluted method was used to measure the susceptibility of6strains of ESBLs-producing E.coli and6strains of the corresponding transconjugants MIC to five P-lactam antibiotics, and selected monomer sensitization to β-lactam antibiotics.2.Two-fold diluted method was used to measure the susceptibility of ESBLs-producing E.coil MIC to the selected monomer, the checkerboard method was used to measure the FIC to monomer combined with various β-lactam antibiotics.3. Dynamic growth assay of effects of various β-lactam antibiotics alone or combined with GA、FR on ESBLs-producing E. coil.4.RT-PCR analysis of the mRNA levels of the main enzyme gene within ESBLs-producing E.coil after the treatments of monomer(FR、GA)、CTX and combine with Suitable concentrations.Conclusions:1.12strains of ESBLs-producing E.coil were nearly highly resistant to β-lactam antibiotics. 2. It was successfully to select fibrauretine and gallic acid can increase susceptibility of ESBLs-producing E.coli to β-lactam antibiotics. But separate fibrauretine, gallic acid had no antimicrobial activity of ESBLs-producing E.coil.3.Fibrauretine widely increased the sensitivity of ESBLs-producing E.coil to β-lactam antibiotics.but the effect of gallic acid no wider than fibrauretine.4.Fibrauretine alone or comined cefotaxime for broad-specrum enzymes blaCTX-M-1G, blaCTX-M-9G of ESBLs-producing E.coil did not significantly affect of the mRNA expression levels.It was possible that Fibrauretinum antibacterial increased sensitization may not be affected by beta-lactamase mRNA expression levels; gallic acid alone or comined cefotaxime for broad-specrum enzymes blaCTX-M-1G of ESBLs-producing E.coil4J did not significantly affect of the mRNA expression levels.but it was able to reduce the blaCTX-M-1G mRNA expression levels that had an obvious effect for the mRNA expression levels of the original strain4blaCTX-M-1G.