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2000
Volume 25, Issue 7
  • ISSN: 1871-5265
  • E-ISSN: 2212-3989

Abstract

Aim

This study was undertaken to compare the proteomic profile of sequential isolates of Beijing lineage () from a patient who developed drug-resistant tuberculosis (TB) during anti-tuberculosis therapy (ATT).

Introduction

Various studies have found the Beijing lineage of strongly associated with multidrug resistance (MDR) development.

Objectives

To identify and characterize the differentially expressed proteins during the drug resistance conversion in Beijing lineage clinical isolates.

Methods

Drug-susceptible and drug-resistant isolates were confirmed as Beijing lineage. The isolates were grown in Middlebrook 7H9 medium for two weeks, and whole-cell lysate was prepared. Two-dimensional gel electrophoresis (2DGE) was used for proteomic analysis, and differentially expressed proteins were identified using MALDI-TOF-MS. Bioinformatics tools were used for molecular docking, phosphorylation, and pupylation site prediction.

Results

Seventeen proteins were found overexpressed in drug-resistant isolates as compared to drug-susceptible isolates, including the six proteins with unknown functions. Molecular docking showed that Isoniazid (INH) and Rifampicin (RIF) interacted with their conserved domains/active sites of these proteins.

Discussion

We characterized two paired clinical isolates from a patient, one being INH and RIF susceptible and other resistant. The comparative analysis of over expressed proteins showed that 5 of 17 proteins belonged to the cell wall and cell processes functional group, 3 to virulence, detoxification, adaptation functional group, and 3 to information pathways functional group, 2 proteins belonged to insertion sequences and phage functional group, and 1 each (Rv0242c, Rv2970c and Rv3208A) to lipid metabolism, intermediary metabolism & respiration and regulatory functional group. We found that the Rv1827, Rv2626c, Rv2714, Rv2970c, Rv3208A, and Rv3881c proteins showed significant interaction with INH and RIF.

Conclusions

These over-expressed proteins probably play an important role in drug resistance development, and further studies on drug resistance mechanisms could provide more details. We also believe that these over-expressed proteins could be used as biomarkers for early prediction of drug-resistance development.

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Proteomic Analysis and Sequential Events During the in-vivo Acquisition of Drug Resistance in Clinical Isolates of Mycobacterium tuberculosis
Infect. Disord. Drug Targets 25, E18715265356091 (2025); https://doi.org/10.2174/0118715265356091250519032548
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  • Article Type:     Research Article
Keyword(s): 2D-gel electrophoresis; Beijing genotype; docking; mass spectrometry; MDR-TB; Proteomics

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