After a screening of more than 700 compounds, the molecule reported as “11326083” showed an antibacterial activity against Mycobacterium abscessus (Mab). The mechanism of action of the selected molecule was investigated by transcriptome analysis to understand how the molecule interacts on the transcription of bacterial genes. These analyses gave an overview of the bacterial up and down-regulated genes after treatment with the “11326083” molecule. Analyses on derivatives and metabolites of “11326083” were also conducted and another promising compound showing an activity against Mab isolated from CF patients and against resistant strains (multidrug-resistant – MDR) and others species of nontuberculous mycobacteria (NTM) was identified.
Recent studies have shown that the bacterial protein MmpL3 is involved in important cellular functions, so the researchers searched for MmpL3 inhibiting molecules. Two compounds acting on MmpL3 protein showed antibacterial properties on Mab, including MDR and other NTM species. In the extension of this project (FFC#14/2020), researchers will deepen the knowledge of the mechanism of action of the most promising compound identified, as well as assessing its bactericidal action in Mab3-infected mice. Furthermore, studies on the MmpL3 protein as a pharmacological target will be conducted.