Synergistic effect of β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli in vitro / 生物工程学报

The widespread of tigecycline resistance gene tet(X4) has a serious impact on the clinical efficacy of tigecycline. The development of effective antibiotic adjuvants to combat the looming tigecycline resistance is needed. The synergistic activity between the natural compound β-thujaplicin and tigecycline in vitro was determined by the checkerboard broth microdilution assay and time-dependent killing curve. The mechanism underlining the synergistic effect between β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli was investigated by determining cell membrane permeability, bacterial intracellular reactive oxygen species (ROS) content, iron content, and tigecycline content. β-thujaplicin exhibited potentiation effect on tigecycline against tet(X4)-positive E. coli in vitro, and presented no significant hemolysis and cytotoxicity within the range of antibacterial concentrations. Mechanistic studies demonstrated that β-thujaplicin significantly increased the permeability of bacterial cell membranes, chelated bacterial intracellular iron, disrupted the iron homeostasis and significantly increased intracellular ROS level. The synergistic effect of β-thujaplicin and tigecycline was identified to be related to interfere with bacterial iron metabolism and facilitate bacterial cell membrane permeability. Our studies provided theoretical and practical data for the application of combined β-thujaplicin with tigecycline in the treatment of tet(X4)-positive E. coli infection.

Synergistic antibacterial effect of association of Callicarpa nudiflora and Vancomycin Hydrochloride towards rat model of MRSA pneumonia / 中草药

Objective: To investigate the synergistic antibacterial effect of Callicarpa nudiflora associated with Vancomycin Hydrochloride on the pneumonia model rats infected by methicillin-resistant staphylococcus aureus (MRSA), and to provide a safer and more effective treatment of clinical ideas for the treatment of infections caused by MRSA. Methods: Totally 80 NIH female rats were randomly divided into eight groups, ten rats as the control group, and 200 μL MRSA (1 × 108 CFU/ mL) bacteria was dropped in the left nasal cavity of the remaining rats to produce infected animal model. The administration with drug respectively by group was continued for 10 d. The common state including activity and intake of water and food were observed and noted. After administration for 10 d, the count of leucocyte, microbial load, and histopathological change of lung were observed. Results: Compared with the model group, the absolute value of leucocyte and microbial load of association of C. nudiflora and Vancomycin Hydrochloride were reduced signicantly (P < 0.05). The pathological damage alleviated significantly. Conclusion: Association of C. nudiflora and Vancomycin Hydrochloride has the synergistic antibacterial effect towards MRSA, which can improve the curative effect of antibiotics and shorten the period of treatment.