Study of isolation of fluoroquinolone-resistant Ureaplasma urealyticum and identification of mutant sites

OBJECTIVE: To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones. METHODS: Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out of 184 clinical isolates and their QRDRs (quinolone resistance-determining region) gyrA, gyrB, parC and parE were amplified by PCR. Sequencing results were compared to those susceptible reference strains and a comparison of deduced amino acid sequences were performed. RESULTS: Sequence comparison revealed a C to A change at 87nt of gyrA QRDR leading to the substitution of Asp95 with glutamic acid and a C to T change at 50nt of parC QRDR leading to the substitution of Ser80 with leucine. CONCLUSION: These results suggest that a C to A change at 87nt of gyrA QRDR and a C to T change at 50nt of parC QRDR are associated with fluoroquinolone resistance of Ureaplasma urealyticum.

Novel berberine derivatives:Design,synthesis,antimicrobial effects,and molecular docking studies

A series of berberine derivatives were synthesized by introducing substituted benzyl groups at C-9.All these synthesized compounds（4a–4m）were screened for their in vitro antibacterial activity against four Gram-positive bacteria and four Gram-negative bacteria and evaluated for their antifungal activity against three pathogenic fungal strains.All these compounds displayed good antibacterial and antifungal activities,compared to reference drugs including Ciprofloxacin and Fluconazole;Compounds 4f,4g,and 4l showed the highest antibacterial and antifungal activities.Moreover,all the synthesized compounds were docked into topoisomerase Ⅱ-DNA complex,which is a crucial drug target for the treatment of microbial infections.Docking results showed that H-bond,π-πstacked,π-cationic,andπ-anionic interactions were responsible for the strong binding of the compounds with the target protein-DNA complex.

Chalcone-Benzotriazole Conjugates as New Potential Antimicrobial Agents： Design, Synthesis, Biological Evaluation and Synergism with Clinical Drugs

A series of chalcone-benzotriazole conjugates as new potential antimicrobial agents were synthesized and char- acterized by ^1H NMR, ^13C NMR, IR and HRMS spectra. Antimicrobial assay manifested that some target com- pounds gave moderate to good antibacterial and antifungal activities. The N- 1 derived benzotriazole 5e and N-2 de- rived benzotriazole 6a exhibited valuable inhibitory efficacy against some tested strains. Especially, derivative 6a gave superior antifungal efficacies against C. utilis, S. cerevisiae and A. flavus （MIC^0.01, 0.02, 0.02 gmol/mL, respectively） to Fluconazole. The drug combination of compound 5e or 6a with antibacterial Chloromycin, Nor- floxacin and antifungal Fluconazole respectively showed stronger antimicrobial efficiency with less dosage and broader antimicrobial spectrum than their separated use alone. The preliminary interaction with calf thymus DNA revealed that compound 6a could intercalate into DNA to form 6a-DNA supramolecular complex which might be a factor to exert its powerful bioactivity. Molecular docking study indicated strong binding of compound 6a with DNA gyrase. The structural parameters such as molecular orbital energy and molecular electrostatic potential of compound 6a were also investigated, which provided better understanding for its good antimicrobial activity.