The evaluation of Phenylalanine-tRNA ligase beta unit (PheT), as a potential target in Mycobacterium abscessus.

Abstract

Mycobacterium abscessus (M. abscessus) is an emerging pathogenic mycobacterium that mainly causes pulmonary infections, especially in immunocompromised patients. This bacterium shows exhibits intrinsic resistance to many anti-tuberculosis drugs, posing significant challenges for both patients and clinicians, thereby raising the need for innovative drug discovery. In this study, we selected phenylalanine-tRNA ligase beta unit (PheT) as a model target and used CRISPR interference to evaluate its essentiality as a therapeutic target against M. abscessus. The results show that genetically disruption of PheT leads to clear growth inhibitory phenotypes both in vitro and in vivo. Further transcriptome analysis revealed differential expression of host genes in response to PheT gene silencing, including genes involved in the cell cycle, apoptotic signaling, and inflammatory responses. Overall, PheT gene plays a crucial role in M. abscessus infection, and its silencing may represent a druggable therapeutic strategy for treating this infection.