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.
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http://dx.doi.org/10.3389/fcimb.2022.959911 | DOI Listing |
BMC Genomics
December 2024
Institute of Aquaculture, University of Stirling, Stirling, Scotland, UK.
Background: The salmon louse (Lepeophtheirus salmonis) is a parasite of wild and farmed salmonid fish, causing huge economic damage to the commercial farming of Atlantic salmon (Salmo salar) in the northern hemisphere. The avermectin emamectin benzoate (EMB) is widely used for salmon delousing. While resistance to EMB is widespread in Atlantic populations of L.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Public Health Agency of Sweden, Solna, Sweden.
This comparative study aimed at qualifying a broth microdilution (BMD) assay for phenotypic drug susceptibility testing (pDST) of complex (MTBC) strains for implementation in a routine DST workflow. The assay was developed based on the EUCAST (European Committee on Antimicrobial Susceptibility Testing) reference protocol for determination of the minimum inhibitory concentration (MIC) of 14 anti-tuberculous drugs (isoniazid [INH], rifampicin [RIF], ethambutol [EMB], amikacin [AMI], moxifloxacin [MFX], levofloxacin [LFX], bedaquiline [BDQ], clofazimine [CFZ], delamanid [DLM], pretomanid [PA], para-aminosalicylic acid [PAS], linezolid [LZD], ethionamide [ETH], and cycloserine [CS]). Forty MTBC strains with various drug resistance profiles were tested to determine the agreement between MIC results and genotypic drug susceptibility testing (gDST) results derived from whole-genome sequencing (WGS).
View Article and Find Full Text PDFJ Infect Public Health
December 2024
Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon. Electronic address:
BMC Infect Dis
December 2024
Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
Background: Efforts toward tuberculosis management and control are challenged by the emergence of Mycobacterium tuberculosis (MTB) resistance to existing anti-TB drugs. This study aimed to explore the potential of machine learning algorithms in predicting drug resistance of four anti-TB drugs (rifampicin, isoniazid, streptomycin, and ethambutol) in MTB using whole-genome sequence and clinical data from Uganda. We also assessed the model's generalizability on another dataset from South Africa.
View Article and Find Full Text PDFImmun Inflamm Dis
November 2024
State Key Laboratory of Respiratory Disease, Guangzhou Key Laboratory of Tuberculosis, Guangzhou Chest Hospital, Institute of Tuberculosis, Guangzhou Medical University, Guangzhou, China.
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