Infection and Drug Resistance (Mar 2021)
Chromone Derivatives CM3a Potently Eradicate Staphylococcus aureus Biofilms by Inhibiting Cell Adherence
Abstract
Qing Zhan,1 Yanlei Xu,1 Lingling Zhan,2 Bingjie Wang,3 Yinjuan Guo,3,4 Xiaocui Wu,3,4 Wenxiu Ai,5 Zengqiang Song,6 Fangyou Yu3,4 1Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, People’s Republic of China; 4Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, People’s Republic of China; 5Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 6School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Fangyou Yu; Zengqiang Song Tel +86-021-65115006; +86-577-86699396Email [email protected]; [email protected]: The ability of Staphylococcus aureus to form biofilms is associated with high mortality and treatment costs. Established biofilms cannot be eradicated by many conventional antibiotics due to the development of antibiotic tolerance by S. aureus. Here we report the synthesis and biological characterization of novel small-molecule compounds with antibiofilm activity. Chromone 5-maleimide substitution compounds (CM3a) showed favorable antibacterial activity against S. aureus.Methods: CM3A with antibacterial activity was synthesized and screened. The minimum inhibitory concentration (MIC) of CM3a were determined by the broth microdilution method. Biofilm eradication assay and colony count methods were used to investigate the effect of CM3a on S. aureus biofilm disruption and killing. Changes in biofilm architecture when subjected to CM3a, were visualized using confocal laser scanning microscopy (CLSM). CCK-8 assay and survival rate of Galleria mellonella larvae were used to test the toxicity of CM3a.Results: The minimum inhibitory concentration (MIC) of CM3a against S. aureus was about 26.4 μM. Biofilm staining and laser scanning confocal microscopy analysis showed that CM3a eradicated S. aureus biofilms by reducing the viability of the constituent bacterial cells. On the other hand, CM3a showed negligible toxicity against mouse alveolar epithelial cells and Galleria mellonella larvae.Conclusion: Chromone derivatives CM3a has therapeutic potential as a safe and effective compound for the treatment of S. aureus infection.Keywords: chromone derivative, maleimide, Staphylococcus aureus, biofilm, eradicate
