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

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Abstract

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.

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ACKNOWLEDGMENTS

For the support and data supply authors would like to express deep thanks to department of Biotechnology, College of Science, University of Anbar.

Funding

This work was supported by ongoing institutional funding. No additional grants to carry out or direct this particular research were obtained.

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Authors and Affiliations

  1. Biotechnology Department, College of Science, University of Anbar, Ramadi-Anbar, Iraq

    Ali Mohammed Al-Rawe & Ahmed AbdulJabbar Suleiman

  2. Ramadi Health Directorate, Ministry of Health, Ramadi-Anbar, Iraq

    Yousif Ibrahem Yousif & Ousama Khalaf Ghareeb Al-Jomaily

  3. Biology Department, College of Sciences, Tikrit University, Tikrit, Iraq

    Semaa A. Shaban

Authors
  1. Ali Mohammed Al-Rawe
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  2. Yousif Ibrahem Yousif
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  3. Ousama Khalaf Ghareeb Al-Jomaily
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  5. Ahmed AbdulJabbar Suleiman
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Correspondence to Ali Mohammed Al-Rawe.

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Al-Rawe, A.M., Yousif, Y.I., Al-Jomaily, O.K. et al. Identification of Antimicrobial Resistance Genes and Drug Targets in Antibiotic-Resistant Clostridioides difficile Clinical Isolates. Mol. Genet. Microbiol. Virol. 38, 197–206 (2023). https://doi.org/10.3103/S0891416823030023

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  • DOI: https://doi.org/10.3103/S0891416823030023

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