KEGG analysis of differentially methylated genes between the streptomycin-resistant and normal groups.

KEGG analysis of differentially methylated genes between the streptomycin-resistant and normal groups.</p

Transcriptome atlas and KEGG analysis of differentially expressed genes between the streptomycin-resistant and normal groups.

A) The heatmap was used to show the differentially expressed genes between the streptomycin-resistant and normal groups. B) KEGG analysis was used to compare the differentially expressed genes in the streptomycin-resistant and normal groups. Rich factor indicated the ratio of the number of differentially expressed genes enriched in each KEGG term to the number of all annotated genes in the KEGG term. Negative binomial distribution model was used to calculate P-value.</p

Differentially methylated genes between the streptomycin-resistant and normal groups.

Differentially methylated genes between the streptomycin-resistant and normal groups.</p

Table_1_mbtD and celA1 association with ethambutol resistance in Mycobacterium tuberculosis: A multiomics analysis.xlsx

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.</p

Up-regulation of I-309, IL-8, and MIG in the serum of active TB patients.

<p>(A-C) quantitative humane cytokine array analysis of peripheral serum samples from health controls (n = 20), individuals with LTBI (n = 20) and patients with active TB (n = 20). Blue, I-309; red, IL-8; yellow, MIG. (D-F) ELISA analysis for the confirmation of I-309, IL-8 and MIG expression in peripheral serum samples from health controls, patients with active TB, and individuals with LTBI or other pulmonary diseases (n = 45 in each group). Mean values ± standard error are shown, * P<0.05; ** P < 0.01 (Student’s <i>t</i>-test).</p

I-309, IL-8 and MIG over-expression is stimulated by Mtb antigens (ESAT-6 and CFP-10) in active TB.

<p>Expression of I-309 (A), IL-8 (B), and MIG (C) induced by PBS or specific TB antigens in whole blood displayed a gradual increase from health controls (n = 80) to individuals with LTBI (n = 45), to those with active TB (n = 80). Mean values ± standard error are shown, *P < 0.05; **P < 0.01 (Student’s <i>t</i>-test).</p

The arrangement of cytokines and antigens on TB-relate cytokine and TB-specific antigen array.

<p>Mouse anti-humane-IgG IgG was used as positive control and BSA were used as negative control.</p

Determination of cut-off values for I-309, IL-8 and MIG in the diagnosis of active TB.

<p>Determination of cut-off values for I-309, IL-8 and MIG in the diagnosis of active TB.</p