HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

mbtD and celA1 association with ethambutol resistance in Mycobacterium tuberculosis: A multiomics analysis.

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 Mycobacterium tuberculosis in vitro 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 (mbtD and celA1) 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 M. tuberculosis using multi-omics profiling. Understanding the epigenetic features associated with EMB resistance may provide new insights into the underlying molecular mechanisms.
AuthorsZhuhua 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
JournalFrontiers in cellular and infection microbiology (Front Cell Infect Microbiol) Vol. 12 Pg. 959911 ( 2022) ISSN: 2235-2988 [Electronic] Switzerland
PMID36118032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022 Wu, Tan, Zhang, Zhao, Liao, Yu, Xu, Wang, Liang, Li, Chen, Chen and Wei.
Chemical References
  • Antitubercular Agents
  • Proteome
  • Ethambutol
  • Serine Proteases
Topics
  • Antitubercular Agents (pharmacology)
  • Drug Resistance, Bacterial (genetics)
  • Ethambutol (pharmacology)
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis (genetics)
  • Proteome
  • Serine Proteases
  • Tuberculosis, Lymph Node

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: