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

TITLE=Antibacterial activity of the novel oxazolidinone contezolid (MRX-I) 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.2023.1225341

DOI=10.3389/fcimb.2023.1225341

ISSN=2235-2988

ABSTRACT=<sec><title>Objective</title><p>To evaluate contezolid (MRX-I) antibacterial activity against <italic>Mycobacterium abscessus in vitro</italic> and <italic>in vivo</italic> and to assess whether MRX-I treatment can prolong survival of infected zebrafish.</p></sec><sec><title>Methods</title><p>MRX-I inhibitory activity against <italic>M. abscessus in vitro</italic> was assessed by injecting MRX-I into zebrafish infected with green fluorescent protein-labelled <italic>M. abscessus</italic>. Thereafter, infected zebrafish were treated with azithromycin (AZM), linezolid (LZD) or MRX-I then maximum tolerated concentrations (MTCs) of drugs were determined based on <italic>M. abscessus</italic> 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.</p></sec><sec><title>Results</title><p>MRX-I anti-<italic>M. abscessus</italic> 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 &lt; 0.01); head: 74147 ± 2175 vs. 95996 ± 8054, p &lt; 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 &gt; 0.05) and the 15.6 μg/mL-treated LZD MTC group (76.67%, p &gt; 0.05) were observed.</p></sec><sec><title>Conclusion</title><p>MRX-I effectively inhibited <italic>M. abscessus</italic> growth and prolonged zebrafish survival when administered to <italic>M. abscessus</italic>-infected zebrafish, thus demonstrating that MRX-I holds promise as a clinical treatment for human <italic>M. abscessus</italic> infections.</p></sec>