Carbon dots (CDs) were synthesized hydrothermally by mixing citric acid (CA) and an antifolic agent, sulfanilamide (SNM), employed for pH sensing and bacterial growth inactivation. Sulfanilamide is a prodrug; aromatic hetero cyclization of the amine moiety along with other chemical modifications produces an active pharmacological compound (chloromycetin and miconazole), mostly administered for the treatment of various microbial infections. On the other hand, the efficacy of the sulfanilamide molecule as a drug for antimicrobial activity was very low. We anticipated that the binding of the sulfanilamide molecule on the carbon dot (CD) surface may form antibacterial CDs. Citric acid was hybridized with sulfanilamide during the hydrothermal preparation of the CDs. The molecular fragments of bioactivated sulfanilamide molecule play a crucial role in bacterial growth inactivation for Gram-positive and Gram-negative bacteria. The functional groups of citric acid and sulfanilamide were conserved during the CD formation, facilitating the zwitterionic behavior of CDs associated with its photophysical activity. At low concentrations of CDs, the antibacterial activity was apparent for Gram-positive bacteria only. This Gram-positive bacteria selectivity was also rationalized by zeta potential measurement.

2023-08-01·European Journal of Medicinal Chemistry

Thiazolyl hydrazineylidenyl indolones as unique potential multitargeting broad-spectrum antimicrobial agents

Article

作者: Zhao, Wen-Hao ; Xu, Jia-He ; Tangadanchu, Vijai Kumar Reddy ; Zhou, Cheng-He

The emergence of pathogenic and drug-resistant microorganisms seriously threatens public safety. This work constructed a unique type of thiazolyl hydrazineylidenyl indolones (THIs) to combat global microbial multidrug-resistance. Bioactive evaluation discovered that some target THIs displayed much superior antimicrobial efficacy than clinical chloromycetin, norfloxacin, cefdinir or fluconazole against the tested strains. Eminently, butyl THI 6c displayed a broad antimicrobial spectrum with low MICs of 0.25-1 μg/mL. The highly active THI 6c not only showed low cytotoxicity and hemolysis, rapidly bactericidal ability, good antibiofilm activity and promising pharmacokinetic properties, but also could significantly impede the development of bacterial resistance. Preliminary exploration of antibacterial mechanism revealed that THI 6c could effectively penetrate the cell membrane of MRSA and embed DNA to form 6c‒DNA supramolecular complex and thus hinder DNA replication. Moreover, THI 6c could reduce cell metabolic activity, which might be attributed to the fact that THI 6c could target the pyruvate kinase of MRSA and interfere with the function of the enzyme. These results provided powerful information for further developing thiazolyl hydrazineylidenyl indolones as new broad-spectrum antimicrobial agents.

2023-01-01·Journal of Biotechnology

A transposon system for random insertion of a gene expression cassette into the chromosome of Bacillus subtilis

Article

作者: Tao, Qing ; Yan, Xin ; Ye, Bin

Bacillus subtilis is a robust industrial workhorse for the production of heterologous proteins. Chromosomal integration-based protein production has advantages over plasmid-based methods. Considering that the expression level of a gene is affected by its location in the chromosome, it is important to find an optimal integration site for the gene to be expressed. This work establishes a method for random insertion of a gene expression cassette into chromosomes, enabling the screening of optimal integration sites for high-level protein production. Specifically, a gene expression cassette and a chloromycetin-resistance marker are assembled into a transposon. This transposon is inserted between the promoter and the ribosomal binding site of the zeocin-resistance marker in the chromosome, which blocks the transcription of the zeocin-resistance gene. Transposase Himar1-mediated transposition of this transposon activates the zeocin-resistance marker, which can be selected on plates containing both chloromycetin and zeocin. The transposition frequency was over 10^-5. This method was used to select proper insertion sites for the expression cassette of methyl parathion hydrolase (MPH). Compared with the common integration site amyE, the expression level of MPH was increased up to 50 % at the yjbH site.

100 项与 Chloramphenicol Sodium Succinate 相关的药物交易

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