Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> Variants
The emergence of antimicrobial resistance (AMR) in <i>Clostridium difficile</i> (<i>C. difficile</i>), particularly to last-line antibiotics such as linezolid, represents a critical challenge in clinical settings. This study investigates the genomic epidemiology of linezolid-...
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| author | Aikaterini Panou Andigoni Malousi Melina Kachrimanidou |
| author_facet | Aikaterini Panou Andigoni Malousi Melina Kachrimanidou |
| author_sort | Aikaterini Panou |
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| description | The emergence of antimicrobial resistance (AMR) in <i>Clostridium difficile</i> (<i>C. difficile</i>), particularly to last-line antibiotics such as linezolid, represents a critical challenge in clinical settings. This study investigates the genomic epidemiology of linezolid-resistant <i>C. difficile</i>, focusing on the distribution and mutational patterns of the chloramphenicol–florfenicol resistance (<i>cfr</i>) gene and its association with multidrug resistance. We analyzed 514 clinical isolates (354 from NCBI Pathogen Detection, 160 from EnteroBase), revealing distinct prevalence patterns among <i>cfr</i> subtypes: <i>cfr</i>(C) was dominant (156/354 NCBI strains; 101/160 EnteroBase strains), whereas <i>cfr</i>(B) frequently harbored missense mutations (p.R247K, p.V294I, and less commonly p.A334T). The <i>cfr</i>(E) subtype was exclusively identified in ribotype 027 (RT027) strains. Notably, <i>cfr</i>(C) exhibited a strong association with RT017, correlating with a conserved 99 bp genomic deletion. Phylogenetic analysis linked <i>cfr</i>-carriage to predominant sequence types (ST1 in NCBI strains, ST37 in EnteroBase isolates). Furthermore, the co-occurrence of <i>cfr</i> with additional AMR genes conferred resistance to macrolides (erythromycin, azithromycin) and tetracyclines, indicating a convergent evolution toward multidrug resistance. These findings underscore the interplay between <i>cfr</i> mutations, hypervirulent ribotypes, and AMR dissemination, necessitating enhanced surveillance to mitigate the spread of resistant <i>C. difficile</i> lineages. |
| format | Article |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-071eb8b15fac490d9eacc1c37b7b3fef2025-08-20T03:27:18ZengMDPI AGBioTech2673-62842025-05-011424210.3390/biotech14020042Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> VariantsAikaterini Panou0Andigoni Malousi1Melina Kachrimanidou2Department of Microbiology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceLaboratory of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Microbiology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceThe emergence of antimicrobial resistance (AMR) in <i>Clostridium difficile</i> (<i>C. difficile</i>), particularly to last-line antibiotics such as linezolid, represents a critical challenge in clinical settings. This study investigates the genomic epidemiology of linezolid-resistant <i>C. difficile</i>, focusing on the distribution and mutational patterns of the chloramphenicol–florfenicol resistance (<i>cfr</i>) gene and its association with multidrug resistance. We analyzed 514 clinical isolates (354 from NCBI Pathogen Detection, 160 from EnteroBase), revealing distinct prevalence patterns among <i>cfr</i> subtypes: <i>cfr</i>(C) was dominant (156/354 NCBI strains; 101/160 EnteroBase strains), whereas <i>cfr</i>(B) frequently harbored missense mutations (p.R247K, p.V294I, and less commonly p.A334T). The <i>cfr</i>(E) subtype was exclusively identified in ribotype 027 (RT027) strains. Notably, <i>cfr</i>(C) exhibited a strong association with RT017, correlating with a conserved 99 bp genomic deletion. Phylogenetic analysis linked <i>cfr</i>-carriage to predominant sequence types (ST1 in NCBI strains, ST37 in EnteroBase isolates). Furthermore, the co-occurrence of <i>cfr</i> with additional AMR genes conferred resistance to macrolides (erythromycin, azithromycin) and tetracyclines, indicating a convergent evolution toward multidrug resistance. These findings underscore the interplay between <i>cfr</i> mutations, hypervirulent ribotypes, and AMR dissemination, necessitating enhanced surveillance to mitigate the spread of resistant <i>C. difficile</i> lineages.https://www.mdpi.com/2673-6284/14/2/42<i>C. difficile</i><i>Cfr</i> subtypesSTlinezolidantimicrobial resistance genes |
| spellingShingle | Aikaterini Panou Andigoni Malousi Melina Kachrimanidou Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> Variants BioTech <i>C. difficile</i> <i>Cfr</i> subtypes ST linezolid antimicrobial resistance genes |
| title | Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> Variants |
| title_full | Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> Variants |
| title_fullStr | Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> Variants |
| title_full_unstemmed | Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> Variants |
| title_short | Genomic Characterization of Linezolid-Resistant <i>Clostridioides difficile</i> Harboring <i>cfr</i> Variants |
| title_sort | genomic characterization of linezolid resistant i clostridioides difficile i harboring i cfr i variants |
| topic | <i>C. difficile</i> <i>Cfr</i> subtypes ST linezolid antimicrobial resistance genes |
| url | https://www.mdpi.com/2673-6284/14/2/42 |
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