Etamycin as a Novel Mycobacterium abscessus Inhibitor

Abstract

The increase in drug-resistant Mycobacterium abscessus, which has become resistant to existing standard-of-care agents, is a major concern, and new antibacterial agents are strongly needed. In this study, we introduced etamycin that showed an excellent activity against M. abscessus. We found that etamycin significantly inhibited the growth of M. abscessus wild-type strain, three subspecies, and clinical isolates in vitro and inhibited the growth of M. abscessus that resides in macrophages without cytotoxicity. Furthermore, the in vivo efficacy of etamycin in the zebrafish (Danio rerio) infection model was greater than that of clarithromycin, which is recommended as the core agent for treating M. abscessus infections. Thus, we concluded that etamycin is a potential anti-M. abscessus candidate for further development as a clinical drug candidate.

A Screening of the MMV Pandemic Response Box Reveals Epetraborole as A New Potent Inhibitor against Mycobacterium abscessus

“…Intracellular activity of ETB was analyzed as previously described [ 44 ]. Briefly, differentiated mBMDMs (7 × 10 5 cells/well) cells were infected with Mab S-mWasabi at a multiplicity of infection (MOI) of 1:1.…”

“…The DMSO was used as negative. The in vivo efficacy of ETB was evaluated by quantification of MabR load in ZF by counting serial dilutions of bacterial CFU as previous described [ 9 , 33 , 44 ] The CFU quantification and survival curve were plotted by GraphPad Prism software using the method from Kaplan and Meier, and log-rank (Mantel–Cox) test respectively.…”

Pipeline of anti‐Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities

“…In addition, a number of marine‐derived compounds also show promising activity against M. abscessus , including etamycin which was first isolated from the culture broth of Streptomyces OPMA1730, plakinamine P, a steroidal alkaloid produced by a Plakina sponge, laurinterol from the red algae Laurencia johnstonii (structures not shown). These compounds may be exploited for further drug design 224‐226 …”

Current Molecular Therapeutic Agents and Drug Candidates for Mycobacterium abscessus

“…Thus, discovering new alternative compounds for Mab infection treatment are urgently needed. In this context, many different screens have been recently performed, such as reporter-based assays, resazurin-based microplate assay and image-based phenotypic screens ( Gupta et al, 2017 ; Jeong et al, 2018 ; Richter et al, 2018 ; Kim et al, 2019 ; Malin et al, 2019 ; Hanh et al, 2020a , 2020b ). However, there is still a poor, promising new chemical lead waiting for clinical trials and market release ( Hanh et al, 2020a ).…”

“…In this context, many different screens have been recently performed, such as reporter-based assays, resazurin-based microplate assay and image-based phenotypic screens ( Gupta et al, 2017 ; Jeong et al, 2018 ; Richter et al, 2018 ; Kim et al, 2019 ; Malin et al, 2019 ; Hanh et al, 2020a , 2020b ). However, there is still a poor, promising new chemical lead waiting for clinical trials and market release ( Hanh et al, 2020a ). This may be because of the intrinsic drug-resistant mechanism that generates the low hit rate for compounds targeting Mab ( Malin et al, 2019 ).…”