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Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
6-Methoxyldihydrochelerythrine Chloride Inhibiting Intra and Extracellular Drug-Resistant Bacteria
Li-Yu Bai1, Zhao-Jie Wang1, Qing-Yu Lu1
1Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650500, People's Republic of China.
None:
Vancomycin-resistant enterococcus (VRE) is a major nosocomial pathogen that exhibits enhanced infectivity due to its robust virulence and biofilm-forming capabilities. In this study, 6-methoxyldihydrochelerythrine chloride (6-MDC) inhibited the growth of exponential-phase VRE and restored VRE's sensitivity to vancomycin. 6-MDC predominantly suppressed the de novo biosynthetic pathway of pyrimidine and purine in VRE by the RNA-Seq analysis, resulting in obstructed DNA synthesis, which subsequently weakened bacterial virulence and impeded intracellular survival. Furthermore, 6-MDC inhibited biofilm formation, eradicated established biofilms, reduced virulence, and enhanced the host immune response to prevent intracellular survival and replication of VRE. Finally, 6-MDC reduced the VRE load in peritoneal fluid and cells significantly in a murine peritoneal infection model. This paper provides insight into the potential antimicrobial target of benzophenanthridine alkaloids for the first time.
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