CRISPR Interference-Based Inhibition of MAB_0055c Expression Alters Drug Sensitivity in Mycobacterium abscessus.

Microbiol Spectr

Division of Life Science, Department of Bio & Medical Big Data (BK21 Four Program), Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.

Published: June 2023

There is an unmet medical need for effective treatments against Mycobacterium abscessus infections. Although advanced molecular genetic tools to validate drug targets and resistance of M. abscessus exist, the practical design and construction of plasmids are relatively laborious and time-consuming. Thus, for this purpose, we used CRISPR interference (CRISPRi) combined with catalytically deactivated Cas9 to inhibit the gene expression of a predicted LysR-type transcriptional regulator gene, , in M. abscessus and evaluated its contribution to the development of drug resistance. Our results showed that silencing the MAB_0055c gene lead to increased rifamycin susceptibility depending on the hydroquinone moiety. These results demonstrate that CRISPRi is an excellent approach for studying drug resistance in M. abscessus. In this study, we utilized CRISPR interference (CRISPRi) to specifically target the gene in M. abscessus, a bacterium that causes difficult-to-treat infections. The study found that silencing the gene lead to increased rifabutin and rifalazil susceptibility. This study is the first to establish a link between the predicted LysR-type transcriptional regulator gene and antibiotic resistance in mycobacteria. These findings underscore the potential of using CRISPRi as a tool for elucidating resistance mechanisms, essential drug targets, and drug mechanisms of action, which could pave the way for more effective treatments for M. abscessus infections. The results of this study could have important implications for the development of new therapeutic options for this challenging-to-treat bacterial infection.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10269454PMC
http://dx.doi.org/10.1128/spectrum.00631-23DOI Listing

Publication Analysis

Top Keywords

mycobacterium abscessus
8
effective treatments
8
abscessus infections
8
drug targets
8
resistance abscessus
8
crispr interference
8
interference crispri
8
predicted lysr-type
8
lysr-type transcriptional
8
transcriptional regulator
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!