AUTHOR=Nie Wenjuan , Gao Shan , Su Lei , Liu Lina , Geng Ruixue , You Yingxia , Chu Naihui 

TITLE=Antibacterial activity of the novel compound Sudapyridine (WX-081) against Mycobacterium abscessus

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1217975

DOI=10.3389/fcimb.2023.1217975

ISSN=2235-2988

ABSTRACT=<sec><title>Objective</title><p>This study aimed to investigate sudapyridine (WX-081) antibacterial activity against <italic>Mycobacterium abscessus in vitro</italic> and its effect on <italic>in vivo</italic> bacterial growth and host survival using a zebrafish model of <italic>M. abscessus</italic> infection.</p></sec><sec><title>Methods</title><p>WX-081 <italic>in vitro</italic> antibacterial activity was assessed based on growth inhibition of <italic>M. abscessus</italic> standard strain ATCC19977 and 36 clinical isolates. Maximum tolerated concentrations (MTCs) of WX-081, bedaquiline, and azithromycin and inhibition of <italic>M. abscessus</italic> growth were assessed <italic>in vivo</italic> 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 <italic>M. abscessus</italic>-infected zebrafish treated with different drug concentrations using a log-rank test, with a p value &lt;0.05 indicating a difference was statistically significant.</p></sec><sec><title>Results</title><p>Drug sensitivity testing of <italic>M. abscessus</italic> standard strain ATCC19977 and 36 clinical isolates revealed MICs ranging from 0.12-0.96 µg/mL and MIC<sub>50</sub> and MIC<sub>90</sub> values of 0.48 µg/mL and 0.96 µg/mL, respectively. Fluorescence intensities of <italic>M. abscessus</italic>-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%.</p></sec><sec><title>Conclusion</title><p>WX-081 effectively inhibited <italic>M. abscessus</italic> growth <italic>in vitro</italic> and <italic>in vivo</italic> and prolonged survival of <italic>M. abscessus</italic>-infected zebrafish, thus indicating that WX-081 holds promise as a clinical treatment for <italic>M. abscessus</italic> infection.</p></sec>