Antibacterial activity of the novel compound Sudapyridine (WX-081) against .

OBJECTIVE

This study aimed to investigate sudapyridine (WX-081) antibacterial activity against and its effect on bacterial growth and host survival using a zebrafish model of infection.

METHODS

WX-081 antibacterial activity was assessed based on growth inhibition of standard strain ATCC19977 and 36 clinical isolates. Maximum tolerated concentrations (MTCs) of WX-081, bedaquiline, and azithromycin and inhibition of growth were assessed after fluorescently labelled bacilli and drugs were injected into zebrafish. Bacterial counts were analysed using one-way ANOVA and fluorescence intensities of zebrafish tissues were analysed and expressed as the mean ± SE. Moreover, Kaplan-Meier survival analysis was conducted to assess intergroup differences in survival of -infected zebrafish treated with different drug concentrations using a log-rank test, with a p value <0.05 indicating a difference was statistically significant.

RESULTS

Drug sensitivity testing of standard strain ATCC19977 and 36 clinical isolates revealed MICs ranging from 0.12-0.96 µg/mL and MIC and MIC values of 0.48 µg/mL and 0.96 µg/mL, respectively. Fluorescence intensities of -infected zebrafish tissues was lower after treatment with the WX-081 MTC (62.5 µg/mL) than after treatment with the azithromycin MTC (62.5 µg/mL) and the bedaquiline MTC (15.6 µg/mL). When the concentration of WX-081 increased from 1.95µg/mL to 1/8 MTC(7.81µg/mL), the survival rate of zebrafish at 4-9 dpf decreased from 90.00% to 81.67%.

CONCLUSION

WX-081 effectively inhibited growth and and prolonged survival of -infected zebrafish, thus indicating that WX-081 holds promise as a clinical treatment for infection.