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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Clinical Infectious Diseases
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1493225
This article is part of the Research Topic Clostridioides difficile Infections and Beyond View all 6 articles

Global Insights into the Genome Dynamics of Clostridioides difficile Associated with Antimicrobial Resistance, Virulence, and Genomic Adaptations among Clonal Lineages

Provisionally accepted
Mohammad Sholeh Mohammad Sholeh 1Masoumeh Beig Masoumeh Beig 1Ebrahim Kouhsari Ebrahim Kouhsari 2Mahdi Rohani Mahdi Rohani 1Farzad Badmasti Farzad Badmasti 1*
  • 1 Pasteur Institute of Iran (PII), Tehran, Iran
  • 2 Golestan University of Medical Sciences, Gorgan, Golestan, Iran

The final, formatted version of the article will be published soon.

    Background: Clostridioides difficile is a significant cause of healthcare-associated infections, with rising antimicrobial resistance complicating treatment. This study offers a genomic analysis of C. difficile, focusing on sequence types (STs), global distribution, antibiotic resistance genes, and virulence factors in its chromosomal and plasmid DNA.Methods: A total of 19,711 C. difficile genomes were retrieved from GenBank. Prokka was used for genome annotation, and multi-locus sequence typing (MLST) identified STs. Pan-genome analysis with Roary identified core and accessory genes. Antibiotic resistance genes, virulence factors, and toxins were detected using the CARD and VFDB databases, and the ABRicate software. Statistical analyses and visualizations were performed in R.Results: Among 366 identified STs, ST1 (1,326 isolates), ST2 (1,141), ST11 (893), and ST42 (763) were predominant. Trends of genome streamlining included reductions in chromosomal length, gene count, protein-coding genes, and pseudogenes. Common antibiotic resistance genes-cdeA (99.46%), cplR (99.63%), and nimB (99.67%)-were nearly ubiquitous. Rare resistance genes like blaCTX-M-2, cfxA3, and blaZ appeared in only 0.005% of genomes. Vancomycin susceptibility-reducing vanG cluster genes were detected at low frequencies. Virulence factors showed variability, with highly prevalent genes such as zmp1 (99.62%), groEL (99.60%), and rpoB/rpoB2 (99.60%). Moderately distributed genes included cwp66 (54.61%) and slpA (79.02%).Toxin genes tcdE (91.26%), tcdC (89.67%), and tcdB (89.06%) were widespread, while binary toxin genes cdtA (26.19%) and cdtB (26.26%) were less common. Toxin gene prevalence, particularly tcdA and tcdB, showed a gradual decline over time, with sharper reductions for cdtA and cdtB. Gene presence patterns (GPP-1) for resistance, virulence, and toxin genes were primarily linked to ST2, ST42, and ST8.This study highlights C. difficile's adaptability and genetic diversity. The decline in toxin genes reflects fewer toxigenic isolates, but the bacterium's increasing preserved resistance factors and virulence genes enable its rapid evolution. ST2, ST42, and ST8 dominate globally, emphasizing the need for ongoing monitoring.

    Keywords: Clostridioides difficile, Genomics, pan-genome analysis, sequence typing, Plasmid, chromosome

    Received: 08 Sep 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Sholeh, Beig, Kouhsari, Rohani and Badmasti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Farzad Badmasti, Pasteur Institute of Iran (PII), Tehran, Iran

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