Identification of Antimicrobial Resistance Genes and Drug Targets in Antibiotic-Resistant Clostridioides difficile Clinical Isolates

• Published in: Molecular genetics, microbiology and virology microbiology and virology, 2023-09, Vol.38 (3), p.197-206
• Main Authors: Al-Rawe, Ali Mohammed, Yousif, Yousif Ibrahem, Al-Jomaily, Ousama Khalaf Ghareeb, Shaban, Semaa A., Suleiman, Ahmed AbdulJabbar
• Format: Article
• Language: English
• Subjects: Anaerobic microorganisms; Antibiotic resistance; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Biomedical and Life Sciences; Clinical isolates; Clostridioides difficile; Diarrhea; Drug resistance; Experimental Papers; Genomes; Infections; Life Sciences; Metronidazole; Microbiology; Molecular Medicine; Mutation; Therapeutic targets; Vancomycin; Whole genome sequencing
• ISSN: 0891-4168; 1934-841X
• DOI: 10.3103/S0891416823030023

Antimicrobial drug resistance has made the treatment of microbial infections quite challenging. A Gram-positive, anaerobic, spore-forming, and toxin-producing bacillus, Clostridioides difficile infection causes diarrhea-related deaths globally. The available drugs like vancomycin and metronidazole are becoming less effective against this infection. We have designed this study to identify genes responsible for antimicrobial resistance and have a better understanding of the mutations and their impact on the antimicrobial resistance activity. The Whole Genome Sequencing data of 11 C. difficile clinical isolates was analyzed to determine novel genes playing a significant role in antimicrobial resistance mechanisms. Comparative structure analysis of wild and mutant structures of proteins and their functions provided insight into the impact of the identified mutations on antimicrobial resistance. We identified 8 genes common in all the isolates that play a vital role in drug resistance through antibiotic efflux, ribosomal protection, and antibiotic inactivation. Variations in the functional domains of tetA(P), tetM, and ermB genes were found to be the most promising novel drug targets. Our findings suggest that these novel gene mutations would be beneficial in designing new drugs to combat C. difficile infection.