Proteomics reveals potential targets for drug-resistant TB

TOPLINE:

Down-regulation of plasma exosome-derived apolipoproteins APOA1, APOB, and APOC1 indicates DR-TB status and lipid metabolism regulation in pathogenesis. 

METHODOLOGY:

• Group case-controlled study assessed 17 drug resistant tuberculosis (DR-TB) and 33 non–drug resistant TB (NDR-TB) patients at The Fourth People’s Hospital of Taiyuan, China, from November 2018 to March 2019.
• Plasma exosome purity and quality was determined by transmission electron microscopy, nanoparticle tracking analysis, and Western blot markers.
• Proteins purified from plasma exosomes were characterized by SDS-Page with Western blotting and liquid chromatography coupled with tandem mass spectrometry techniques.
• Functional proteomic differential analysis was achieved using the UniProt-GOA, Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING databases.

TAKEAWAYS:

• DR-TB patients tended to be older than NDR-TB patients.
• Isolated plasma exosomes were morphologically characterized as being "close to pure."
• Differential gene expression analysis revealed 16 up-regulated and 10 down-regulated proteins from DR-TB compared with NDR-TB patient-derived plasma exosomes.
• Protein-protein interaction modeling suggests that down-regulated apolipoproteins APOA1, APOB, and APOC1 have a role in mediating DR-TB development through their functions in lipid metabolism and protein transport.

IN PRACTICE:

Key apolipoproteins "may be involved in the pathogenesis of DR-TB via accelerating the formation of foamy macrophages and reducing the cellular uptake of anti-TB drugs." 

STUDY DETAILS:

The study led by Mingrui Wu, of Shanxi Medical University, Shanxi, China, and colleagues was published in the July 2023 issue of Tuberculosis.

LIMITATIONS:

This study is limited by an enrollment bias of at least twice as many men to women patients for both DR-TB and NDR-TB categories, reporting of some incomplete data collection characterizing the study population, and small sample size, which did not permit stratified analysis of the five types of DR-TB.

DISCLOSURES:

The authors report no relevant financial relationships.

Source: Medscape