Evaluation of cellular response to Clostridium difficile toxin-A: a network analysis

Gastroenterol Hepatol Bed Bench. 2022;15(4):421-425. doi: 10.22037/ghfbb.v15i4.2634.

Abstract

Aim: The current study aimed to determine crucial genes targeted by toxin-A through network analysis.

Background: Clostridium difficile (C difficile) produces toxin-A and toxin-B and is known as a risk factor for hospital infection, especially after broad spectrum antibiotic therapy. Bioinformatics findings have led to the introduction of a set of genes and biological terms that are targeted by toxin-B in colon epithelia.

Methods: The significant differentially expressed genes (DEGs) of human intestinal Caco-2 cells treated by toxin-A versus control were retrieved from gene expression omnibus (GEO). The queried DEGs were analyzed using by protein-protein interaction (PPI) network analysis through STRING database and Cytoscape software v.3.7.2.

Results: Among 157 significant DEGs, JUN, VEGFA, CDKN1A, ATF3, SNAI1, DUSP1, HSPB1, MCL1, KLF4, FOSL1, HSPA1A, and SQSTM1 were determined as hubs and JUN, DUSP1, DUSP5, EZR, MAP1LC3B, and SQSTM1 were highlighted as bottlenecks.

Conclusion: JUN, DUSP1, and SQSTM1 are possible drug targets to prevent and treat C difficile infection.

Keywords: Clostridium difficile; Drug target; Infection; Network analysis; Treatment.