Publication
Title
Mycothione reductase as a potential target in the fight against Mycobacterium abscessus infections
Author
Abstract
While infections caused by Mycobacterium abscessus complex (MABC) are rising worldwide, the current treatment of these infections is far from ideal due to its numerous shortcomings thereby increasing the urge for novel drug targets. In this study, mycothione reductase (Mtr) was evaluated for its potential as a drug target for MABC infections since it is a key enzyme needed in the recycling of mycothiol, the main low-molecular-weight thiol protecting the bacteria against reactive oxygen species and other reactive intermediates. First, a Mab increment mtr mutant strain was generated, lacking mtr expression. Next, the in vitro sensitivity of Mab increment mtr to oxidative stress and antimycobacterial drugs was determined. Finally, we evaluated the intramacrophage survival and the virulence of Mab increment mtr in Galleria mellonella larvae. Mab increment mtr demonstrated a 39.5-fold reduction in IC90 when exposed to bedaquiline in vitro. Furthermore, the Mab increment mtr mutant showed a decreased ability to proliferate inside macrophages and larvae, suggesting that Mtr plays an important role during MABC infection. Altogether, these findings support the assumption of Mtr being a potential target for antimycobacterial drugs.
Language
English
Source (journal)
mSphere / American Society for Microbiology. - Washington D.C., 2016, currens
Publication
Washington : Amer soc microbiology , 2023
ISSN
2379-5042
DOI
10.1128/MSPHERE.00669-23
Volume/pages
(2023) , p. 1-14
ISI
001123958000001
Pubmed ID
38085034
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Exploitation of key enzymes of the mycothiol biosynthesis to improve treatment of mycobacterium avium complex infections.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 09.01.2024
Last edited 12.01.2024
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