Global insights into the genome dynamics of Clostridioides difficile associated with antimicrobial resistance, virulence, and genomic adaptations among clonal lineages.
Mohammad Sholeh, Masoumeh Beig, Ebrahim Kouhsari, Mahdi Rohani, Mohammad Katouli, Farzad Badmasti
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引用次数: 0
Abstract
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.
Conclusion: 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.
期刊介绍：
Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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