Gene network interaction analysis to elucidate the antimicrobial resistance mechanisms in the Clostridiumdifficile

• Published in: Microbial pathogenesis 2023-05, Vol.178, p.106083-106083, Article 106083
• Main Authors: Anusha, M., Tejaswini, V., Udhaya Kumar, S., Prashantha, C.N., Vasudevan, Karthick, George Priya Doss, C.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - pharmacology; Azithromycin; Clostridioides difficile - genetics; Clostridium difficile; Clustering analysis; Drug Resistance, Bacterial - genetics; Erythromycin; Functional enrichment analysis; Gene ontology; Gene Regulatory Networks; Microbial Sensitivity Tests; Rifampin; Topological parameters
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2023.106083

Antimicrobial resistance has caused chaos worldwide due to the depiction of multidrug-resistant (MDR) infective microorganisms. A thorough examination of antimicrobial resistance (AMR) genes and associated resistant mechanisms is vital to solving this problem. Clostridium difficile (C. difficile) is an opportunistic nosocomial bacterial strain that has acquired exogenous AMR genes that confer resistance to antimicrobials such as erythromycin, azithromycin, clarithromycin, rifampicin, moxifloxacin, fluoroquinolones, vancomycin, and others. A network of interactions, including 20 AMR genes, was created and analyzed. In functional enrichment analysis, Cellular components (CC), Molecular Functions (MF), and Biological Processes (BP) were discovered to have substantial involvement. Mutations in the rpl genes, which encode ribosomal proteins, confer resistance in Gram-positive bacteria. Full erythromycin and azithromycin cross-resistance can be conferred if more than one of the abovementioned genes is present. In the enriched BP, rps genes related to transcriptional regulation and biosynthesis were found. The genes belong to the rpoB gene family, which has previously been related to rifampicin resistance. The genes rpoB, gyrA, gyrB, rpoS, rpl genes, rps genes, and Van genes are thought to be the hub genes implicated in resistance in C. difficile. As a result, new medications could be developed using these genes. Overall, our observations provide a thorough understanding of C. difficile AMR mechanisms. •Antimicrobial resistance is a global problem that requires understanding of AMR genes and mechanisms.•C. difficile is a bacterial strain that has acquired exogenous AMR genes, leading to resistance to multiple antimicrobials.•The 20 genes in C. difficile revealed significant transcriptional regulation, biosynthesis, and rifampicin resistance in AMR.•Mutations in rpl genes can lead to cross-resistance to erythromycin and azithromycin if more than one gene is present.•rpoB, gyrA, gyrB, rpoS, rpl, rps, and van are hub genes implicated in C. difficile resistance.•These could be targeted for developing new medications to combat AMR.