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

IF 2.8 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2025-03-01 DOI:10.1016/j.tube.2025.102626

Weile Xie , Dan Luo , Mingqing Wu , Yicheng Sun , Zhe Wang

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引用次数: 0

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.

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.