and Association with Ethambutol Resistance in : A Multiomics Analysis

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2022 Sep 19

PMID 36118032

Authors

Zhuhua Wu

Qiuchan Tan

Chenchen Zhang

Yuchuan Zhao

Qinghua Liao

Meiling Yu

Liuyue Xu

Jiawen Wang

Hongdi Liang

Haicheng Li

Liang Chen

Xunxun Chen

Wenjing Wei

Affiliations

Soon will be listed here.

Abstract

Ethambutol (EMB) is a first-line antituberculosis drug currently being used clinically to treat tuberculosis. Mutations in the embCAB operon are responsible for EMB resistance. However, the discrepancies between genotypic and phenotypic EMB resistance have attracted much attention. We induced EMB resistance in and used an integrated genome-methylome-transcriptome-proteome approach to study the microevolutionary mechanism of EMB resistance. We identified 509 aberrantly methylated genes (313 hypermethylated genes and 196 hypomethylated genes). Moreover, some hypermethylated and hypomethylated genes were identified using RNA-seq profiling. Correlation analysis revealed that the differential methylation of genes was negatively correlated with transcription levels in EMB-resistant strains. Additionally, two hypermethylated candidate genes ( and ) were screened by iTRAQ-based quantitative proteomics analysis, verified by qPCR, and corresponded with DNA methylation differences. This is the first report that identifies EMB resistance-related genes in laboratory-induced mono-EMB-resistant using multi-omics profiling. Understanding the epigenetic features associated with EMB resistance may provide new insights into the underlying molecular mechanisms.

Citing Articles

Multidrug-resistant tuberculosis.

Dheda K, Mirzayev F, Cirillo D, Udwadia Z, Dooley K, Chang K Nat Rev Dis Primers. 2024; 10(1):22.

PMID: 38523140 DOI: 10.1038/s41572-024-00504-2.

The acetylation of pknH is linked to the ethambutol resistance of Mycobacterium tuberculosis.

Sun Q, Zou Y, Feng Q, Gong Z, Song M, Li M Arch Microbiol. 2023; 205(10):337.

PMID: 37740776 DOI: 10.1007/s00203-023-03676-9.

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