Impact of bedaquiline and capreomycin on the gene expression patterns of multidrug‐resistant Mycobacterium tuberculosis H37Rv strain and understanding the molecular mechanism of antibiotic resistance

Abstract

The emergence of multidrug resistance (MDR), extensively drug‐resistant, and total drug‐resistant Mycobacterium tuberculosis (Mtb) strains have hampered the treatment of tuberculosis (TB). Capreomycin and Bedaquiline are currently used for MDR‐TB treatment. To understand the impact of these antibiotics on Mtb genes, we have curated the gene expression data where the Mtb cultures were exposed to the Bedaquiline and Capreomycin. Based on the P value cut off (<0.05) and logFC (<−0.5 and >+0.5) values, we have selected the top differentially expressed genes during the antibiotic exposures. We have observed that the top differentially expressed Mtb genes were related to universal stress genes, two‐component regulatory systems, and drug efflux pumps. We have curated the Mtb gene datasets and carried out the functional over‐representation analysis using the individual gene expression values. We further, constructed the gene interaction networks of antibiotic resistance genes and virulence genes of Mtb to understand the impact of the antibiotics at the molecular level and thus to understand the antimicrobial resistance and virulence patterns. Our study elucidates the impact of antibiotics on the Mtb genes at the molecular level and the positively enriched pathways, operons, and regulons data are helpful in understanding the resistance patterns in Mtb. The upregulated genes during the exposure of Bedaquiline and Capreomycin can be considered as potent drug targets for the development of new anti‐TB drugs.

Abattoir survey of bovine tuberculosis in tanta, centre of the Nile delta, with in silico analysis of gene mutations and protein–protein interactions of the involved mycobacteria

“…Similarly, Miryala et al. (2019) performed gene interaction network analysis and enrichment analysis and reported rpoB, rpsL, gyrA and gyrB in one cluster as antibiotic resistant genes with high number of functional interactors that may play the key role in pathogenic virulence and antibiotic resistance. embA, embB and embC are the key enzymes responsible for biogenesis of arabinogalactan and lipoarabinomannan, the two major constituents of the mycobacterial cell wall (Singh et al., 2019).…”

“…The interactions between rpoA, rpoB and rpoC subunits are known, and it had been proposed that rpoB mutations in rifampicin-resistant Mtb mutants come with a fitness cost while mutations in rpoA or rpoC are F I G U R E 7 Bipartite graph represents the rpoC gene and relevant source mutations and chromosome position; blue circles represent the amino acids mutations proposed to compensate this fitness cost(Xu et al, 2018). Similarly,Miryala et al (2019) performed gene interaction network analysis and enrichment analysis and reported rpoB, rpsL, gyrA and gyrB in one cluster as antibiotic resistant genes with high number of functional interactors that may play the key role in pathogenic virulence and antibiotic resistance. embA, embB and embC are the key enzymes responsible for biogenesis of arabinogalactan and lipoarabinomannan, the two major constituents of the mycobacterial cell wall(Singh et al, 2019).…”

A Novel Risk Factor Model Based on Glycolysis-Associated Genes for Predicting the Prognosis of Patients With Prostate Cancer

“…PCa gene expression data (RNA-Seq) and the corresponding clinical data were downloaded from the TCGA database (https:// portal.gdc.cancer.gov) and Gene Expression Omnibus (GEO: https://www.ncbi.nlm.nih.gov/geo/). With |log 2 (fold change)| >0.5 and false discovery rate (FDR) <0.05 as the standards (22), the data were standardized with the "edgeR" package of R software (version 3.6.3, https://www.r-project.org), and then differential expression analysis was performed. The glycolysis-related gene dataset was downloaded from GSEA (http://www.…”

The Involvement of Mycobacterium Type III-A CRISPR-Cas System in Oxidative Stress

“…A recent study demonstrated that deletion of cpnB , which encodes a multifunctional protein that hydrolyzes c-di-AMP, c-di-GMP, and nanoRNAs, upregulated all the cas (CRISPR-associated) genes compared to the WT ( Zhang et al, 2018 ). Of note, the expression of cas gene varies in response to environmental stresses, such as oxidative stress and antibiotic treatment ( Miryala et al, 2019 ), suggesting a link between the activity of type III-A CRISPR-Cas and stresses. Indeed, it has been reported that overexpression of cas genes impacts mycobacterial physiology ( Huang et al, 2016 ; Zhai et al, 2018 ; Wei et al, 2019 ).…”