Antibacterial activity of the novel oxazolidinone contezolid (MRX-I) against Mycobacterium abscessus

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Wenjuan. Nie¹  Shan. Gao¹  Naihui Chu¹  Lei. Su²  Lina. Liu³  Ruixue. Geng⁴  Yingxia. You⁵ 

[1] Tuberculosis Department, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China;Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China;Tuberculosis Department, Henan Province Anyang City Tuberculosis Prevention and Control Institute, Anyang, China;Tuberculosis Department, Hengshui Third People’s Hospital, Hengshui, China;Tuberculosis Department, Hohhot Second Hospital, Hohhot, China;Tuberculosis Department, Zhengzhou Sixth People’s Hospital, Zhengzhou, China;

关键词: Mycobacterium abscessus;    contezolid;    zebrafish;    activity;    in vivo;   

DOI  :  10.3389/fcimb.2023.1225341

 received in 2023-05-19, accepted in 2023-07-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveTo 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.MethodsMRX-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.ResultsMRX-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.ConclusionMRX-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.

【 授权许可】

Unknown   
Copyright © 2023 Gao, Nie, Liu, Su, You, Geng and Chu