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Ringo, Herieth Heriel

University of British Columbia

Non-tuberculous mycobacteria (NTM) are comprised of more than 190 species, broadly characterized as slowly or rapidly growing mycobacteria (SGM/RGM). In the RGM group, Mycobacterium abscessus (MAB) is the leading cause of NTM pulmonary diseases among individuals with pre-existing lung diseases like cystic fibrosis. The mode of transmission is not fully understood. MAB is extremely resistant to antibiotics, which leads to a long and often unsuccessful treatment. Even worse, there are no FDA approved drugs against MAB. Hence, these challenges highlight the urgent need to develop effective MAB antibiotics. Here I describe a collaborative work involving phenotypic screening of natural extracts and pure compounds libraries against MAB in broth and in human macrophages. The libraries were Traditional Chinese Medicine (TCM), marine extracts (ME), pure marine compounds (PMC), and Global Health Priority Box (GHP). We identified seven pure active compounds in broth which displayed a dose-dependent mechanism of inhibition. Also, we found three intracellularly active fractions, which are currently undergoing bioassay guided fractionation to isolate pure active compounds. The seven active compounds in broth had cytotoxicity profiles with varying selectivity to MAB compared to HEK293T cells and three of these compounds indicated a selective growth inhibition against mycobacteria and Gram-positive bacteria. Further work needs to be done to improve the antimycobacterial activities and cytotoxicity profiles of these active compounds. The present study contributes to the ongoing drug discovery initiatives to reduce the burden of MAB infections among individuals most in need. Advanced studies of our active compounds have the potential to discover novel tools for the effective treatment against MAB infections.

Text

2024-08-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89117

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/