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Updated: Aug 11, 2025
Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Multidrug-resistant toxigenic Corynebacterium diphtheriae sublineage 453 with two novel resistance genomic islands
Gabriele Arcari1,2, Mélanie Hennart1,3, Edgar Badell1,4
1Institut Pasteur, Université Paris Cité, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France.
Abstract:
Antimicrobial therapy is important for case management of diphtheria, but knowledge on the emergence of multidrug-resistance in Corynebacterium diphtheriae is scarce. We report on the genomic features of two multidrug-resistant toxigenic isolates sampled from wounds in France 3 years apart. Both isolates were resistant to spiramycin, clindamycin, tetracycline, kanamycin and trimethoprim-sulfamethoxazole. Genes ermX, cmx, aph(3')-Ib, aph(6)-Id, aph(3')-Ic, aadA1, dfrA15, sul1, cmlA, cmlR and tet(33) were clustered in two genomic islands, one consisting of two transposons and one integron, the other being flanked by two IS6100 insertion sequences. One isolate additionally presented mutations in gyrA and rpoB and was resistant to ciprofloxacin and rifampicin. Both isolates belonged to sublineage 453 (SL453), together with 25 isolates from 11 other countries (https://bigsdb.pasteur.fr/diphtheria/). SL453 is a cosmopolitan toxigenic sublineage of C. diphtheriae, a subset of which acquired multidrug resistance. Even though penicillin, amoxicillin and erythromycin, recommended as the first line in the treatment of diphtheria, remain active, surveillance of diphtheria should consider the risk of dissemination of multidrug-resistant strains and their genetic elements.
Insights
Multidrug-resistant diphtheria strains carrying resistance genes on genomic islands have emerged. Continued surveillance is crucial to monitor the spread of these resistant Corynebacterium diphtheriae strains.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Antimicrobial therapy is key for diphtheria management.
- Limited data exists on multidrug resistance in Corynebacterium diphtheriae.
Purpose of the Study:
- To investigate the genomic characteristics of multidrug-resistant toxigenic Corynebacterium diphtheriae isolates.
- To understand the genetic basis of multidrug resistance in these strains.
Main Methods:
- Whole-genome sequencing of two multidrug-resistant toxigenic Corynebacterium diphtheriae isolates.
- Analysis of antimicrobial resistance genes and their genomic context.
- Phylogenetic analysis to determine isolate lineage.
Main Results:
- Two toxigenic Corynebacterium diphtheriae isolates exhibited resistance to multiple antibiotics, including spiramycin, clindamycin, tetracycline, kanamycin, and trimethoprim-sulfamethoxazole.
- Resistance genes were located on two distinct genomic islands, involving transposons, an integron, and insertion sequences.
- One isolate also showed resistance to ciprofloxacin and rifampicin due to mutations in gyrA and rpoB.
- Both isolates belonged to the cosmopolitan sublineage 453 (SL453), a subset of which has acquired multidrug resistance.
Conclusions:
- Multidrug resistance in toxigenic Corynebacterium diphtheriae is associated with specific genomic islands.
- The cosmopolitan SL453 sublineage harbors multidrug-resistant strains.
- Enhanced surveillance for multidrug-resistant diphtheria strains and their genetic elements is recommended.
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