ABSTRACT
Staphylococcus aureus, a common gram-positive pathogenic bacterium, is a main cause of hospital infection. The prevalence rate of methicillin-resistant S. aureus (MRSA) has made its treatment difficult in recent decades. Moreover, S. aureus in the highly tolerant format of biofilm or persister often renders infections refractory. Thus, developing new active compounds against resistant S. aureus is urgently needed. In this study, by a high-throughput screening assay, we identified a small molecule, L007-0069, that exhibited strong and effective bactericidal activity against S. aureus and its high resistance patterns, such as biofilms and persisters, with a low probability of inducing resistance. By molecular dynamics and fluorescent probe analysis, mechanistic studies revealed that the bactericidal activity of L007-0069 was mainly mediated by membrane disruption and metabolic disorder induction. Furthermore, L007-0069 showed effective anti-MRSA effects in vivo in both a wound infection model and a peritonitis-sepsis model, with no detectable toxicity observed at the therapeutic dosage. In conclusion, L007-0069 has the potential to become an alternative for the treatment of highly resistant S. aureus-related infections.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Biofilms , Fluorescent Dyes , Humans , Microbial Sensitivity Tests , Phenotype , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureusABSTRACT
Objective:To investigate the effect of small molecule antibacterial agent Halicin against Staphylococcus aureus. Methods:The minimum inhibitory concentration (MIC) and minimum bactericidal concentration of Halicin against S. aureus were detected by the microbroth dilution method. The time-kill assay of Halicin against S. aureus was detected by agar plate dilution method. Micro checkerboard dilution method was used to determine the synergistic antibacterial activity between Halicin and conventional antibiotics. Crystal violet staining method was used to assess the biofilm inhibitory and eradicating activity of Halicin. Hemolysis rate was used to detect the mammal cell toxicity of Halicin. Through the mouse skin abscess model, take the skin tissue around the abscess to grind and dilute the colony to detect the antibacterial effect of Halicin in vivo. Results:Halicin showed significant bacteriostasis effects against S. aureus with the minimum inhibitory concentration of 2-4 mg/L. Halicin could significantly reduce the average CFU counts of S. aureus about 5.5×10 6 CFU/ml in a concentration-dependent manner after 8 h treatment at the concentration of 16 mg/L. The fractional inhibitory concentration value between Halicin and ampicillin was 0.5, showing a synergistic antibacterial efficacy. Halicin effectively inhibited the formation of biofilms at the concentration of 4 × MIC, reducing the total biofilm biomass ( A570) from (2.89±0.09) to (1.35±0.17) ( t=11.12, P<0.05). However, there was no eradication effect against preformed biofilms. In addition, Halicin had almost no hemolytic activity on red blood cells even at the concentration up to 128 mg/L. It showed that 20 mg/kg Halicin reduced bacterial burden about 3.0×10 7 CFU/ml in vivo. Conclusion:Halicin had a strong antimicrobial activity against S. aureus with no hemolytic activity.
ABSTRACT
Objective To explore the effect of experimental design in the experimental teaching of fundamental nursing. Methods 168 and 199 baccalaureate nursing students were in the control and experimental group respectively, the control group received traditional experimental teaching method, and the experimental group must complete the experimental design before entering the lab. The teaching effect between the two groups were compared. Results The mean operation score of the experimental group was significantly higher than the control group, the proportion of those students who reflected their teaching method could enhance creative ability, problem-solving ability and practical ability was higher in the experimental group, 100% teachers reflected experimental design could improve operation level, strengthen theoretical knowledge, animate teaching atmosphere. Conclusions Experimental design could arouse students' enthusiasm and initiative to study, advocate them to think and ask.
ABSTRACT
AIM:To determine the contents of sinomenine and chelidonine in Tong’an Injection(Caulis sinomenii, Chelidonium majus Linn, etc). METHODS: HPLC was used. The conditions included the gradient elution with methanol-0.1% triethylamine. The detection wavelength was set at 280 nm. RESULTS: The calibration curve was linear in the range of 162-1 620 ?g for the sinomenine and the range of 35-350 ?g for chelidonine, respectively. The average recovery for sinomenine was 99.56% and the relative standard deviation was 0.41%(n=5). The average recovery for chelidonine was 99.46% and the relative standard deviation was 0.62% (n=5). CONCLUSION: The method is simple, rapid and specialty. It can be used for the determination of sinomenine and chelidonine in Tong’an Injection.
