Objective To evaluate contezolid (MRX-I) antibacterial activity against Mycobacterium abscessus in vitro and in vivo and to assess whether MRX-I treatment can prolong survival of infected zebrafish. Methods MRX-I inhibitory activity against M. abscessus in vitro was assessed by injecting MRX-I into zebrafish infected with green fluorescent protein-labelled M. abscessus . Thereafter, infected zebrafish were treated with azithromycin (AZM), linezolid (LZD) or MRX-I then maximum tolerated concentrations (MTCs) of drugs were determined based on M. abscessus growth inhibition using one-way ANOVA. Linear trend analysis of CFU counts and fluorescence intensities (mean ± SE values) was performed to detect linear relationships between MRX-I, AZM and LZD concentrations and these parameters. Results MRX-I anti- M. abscessus minimum inhibitory concentration (MIC) and MTC were 16 μg/mL and 15.6 μg/mL, respectively. MRX-I MTC-treated zebrafish fluorescence intensities were significantly lower than respective LZD group intensities (whole-body: 439040 ± 3647 vs. 509184 ± 23064, p < 0.01); head: 74147 ± 2175 vs. 95996 ± 8054, p < 0.05). As MRX-I concentration was increased from 0.488 μg/mL to 15.6 μg/mL, zebrafish whole-body, head and heart fluorescence intensities decreased. Statistically insignificant differences between the MRX-I MTC group survival rate (78.33%) vs. corresponding rates of the 62.5 μg/mL-treated AZM MTC group (88.33%, p > 0.05) and the 15.6 μg/mL-treated LZD MTC group (76.67%, p > 0.05) were observed. Conclusion MRX-I effectively inhibited M. abscessus growth and prolonged zebrafish survival when administered to M. abscessus -infected zebrafish, thus demonstrating that MRX-I holds promise as a clinical treatment for human M. abscessus infections.
Huang Jiaqing,Liu Cenwei,Price Gordon W.,Wang Yixiang
Bacillus cellulasensis Zn-B isolated from vegetable soil was highly adaptable to Zinc (Zn) and Cadmium (Cd). Cd, but not Zn, adversely affected the total protein spectrum and functional groups of Bacillus cellulasensis Zn-B. Up to 31 metabolic pathways and 216 metabolites of Bacillus cellulasensis Zn-B were significantly changed by Zn and Cd (Zn&Cd). Some metabolic pathways and metabolites related to functional groups of sulfhydryl (-SH) and amine (-NH-) metabolism were enhanced by Zn&Cd addition. The cellulase activity of Bacillus cellulasensis Zn-B was up to 8.58 U mL −1 , increased to 10.77 U mL −1 in Bacillus cellulasensis Zn-B + 300 mg L −1 Zn, and maintained at 6.13 U mL −1 in Bacillus cellulasensis Zn-B + 50 mg L −1 Cd. The vegetables’ cellulose content was decreased by 25.05–52.37% and 40.28–70.70% under the action of Bacillus cellulasensis Zn-B and Bacillus cellulasensis Zn-B + 300 mg L −1 Zn. Those results demonstrated that Zn could significantly enhance cellulase activity and biodegradability of Bacillus cellulasensis Zn-B to vegetable cellulose. Bacillus cellulasensis Zn-B can survive in vegetable soil accumulated with Zn&Cd. The tolerance concentration and adsorption capacity of Bacillus cellulasensis Zn-B to Zn were up to 300 mg L −1 and 56.85%, indicating that Bacillus cellulasensis Zn-B acting as a thermostability biological agent had an essential advantage in accelerating the degradation of discarded vegetables by Zn and were beneficial to maintain organic matter content of vegetable soil. Graphical Abstract
危险品化学品经营许可证（带存储）