Identification of active compounds against Mycobacterium abscessus
department or school: Science, Faculty of
department or school: Microbiology and Immunology, Department of
data provider: DSpace
degree campus: UBCV
creator: Ringo, Herieth Heriel
issued: 2024-08-30T15:03:17Z
issued: 2024
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: 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.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/89117
note: IDENTIFICATION OF ACTIVE COMPOUNDS AGAINST MYCOBACTERIUM ABSCESSUS by Herieth Heriel Ringo B.Sc., Quest University Canada, 2018 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in The Faculty of Graduate and Postdoctoral Studies (Microbiology and Immunology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2024 © Herieth Heriel Ringo, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Identification of active compounds against Mycobacterium abscessus submitted by Herieth Heriel Ringo in partial fulfilment of the requirements for the degree of Master of Science in Microbiology and Immunology Examining Committee: Dr. Yossef Av-Gay, Professor, Microbiology and Immunology, UBC Supervisor Dr. Elitza I. Tocheva, Assistant Professor, Microbiology and Immunology, UBC Supervisory Committee Member Dr. Jim Sun, Assistant Professor, Microbiology and Immunology, UBC Additional Examiner Additional Supervisory Committee Members: Dr. Lindsay Eltis, Professor, Microbiology and Immunology, UBC Supervisory Committee Member iii Abstract 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 Tradi…
has type: Thesis/Dissertation
date issued: 2024-11
is shown at: 10.14288/1.0445263
language: eng
degree discipline: Microbiology and Immunology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Av-Gay, Yossef
type: Text
identifier URI: http://hdl.handle.net/2429/89117