Metabolic perturbation reduces antibiotic tolerance in Mycobacterium tuberculosis.

IF 3.5 4区生物学 Q3 MICROBIOLOGY

Microbiology-Sgm Pub Date : 2026-04-01 DOI:10.1099/mic.0.001697

Chen-Yi Cheung, Imogen Samuels, Hannah R Klaus, Gregory M Cook, Matthew B McNeil

引用次数: 0

Abstract

Mycobacterium tuberculosis is tolerant to many antibiotics, leading to impaired antibiotic killing. Using CRISPR interference (CRISPRi) transcriptional knockdowns, we generated a panel of metabolically compromised strains to identify tolerance pathways for pursuing in therapeutic development. Disrupting the regulation of intracellular iron storage, amino acid biosynthesis and redox defence mechanisms potentiated the lethality of multiple drugs and translated to infected THP-1 macrophages. This work reinforces the role of metabolism as a major contributor to drug tolerance in M. tuberculosis.

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代谢紊乱降低结核分枝杆菌的抗生素耐受性。

结核分枝杆菌对许多抗生素具有耐受性，导致抗生素杀伤能力受损。利用CRISPR干扰（CRISPRi）转录敲低，我们生成了一组代谢受损的菌株，以确定治疗开发中追求的耐受性途径。破坏细胞内铁储存、氨基酸生物合成和氧化还原防御机制的调节，增强了多种药物的致命性，并转化为感染的THP-1巨噬细胞。这项工作加强了代谢作为结核分枝杆菌耐药的主要贡献者的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microbiology-Sgm 生物-微生物学

CiteScore

4.60

自引率

7.10%

发文量

132

审稿时长

3.0 months

期刊介绍： We publish high-quality original research on bacteria, fungi, protists, archaea, algae, parasites and other microscopic life forms. Topics include but are not limited to: Antimicrobials and antimicrobial resistance Bacteriology and parasitology Biochemistry and biophysics Biofilms and biological systems Biotechnology and bioremediation Cell biology and signalling Chemical biology Cross-disciplinary work Ecology and environmental microbiology Food microbiology Genetics Host–microbe interactions Microbial methods and techniques Microscopy and imaging Omics, including genomics, proteomics and metabolomics Physiology and metabolism Systems biology and synthetic biology The microbiome.