1887

Microbial Genomics logo

Volume 9, Issue 1

Multidrug-resistant toxigenic sublineage 453 with two novel resistance genomic islands Open Access

Abstract

Antimicrobial therapy is important for case management of diphtheria, but knowledge on the emergence of multidrug-resistance in 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 and ) 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 and 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 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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Corynebacterium diphtheriae , diphtheria , genomic epidemiology , multidrug-resistance , phylogeography and toxigenic strains
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000923
2023-01-27
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/mgen/9/1/mgen000923.html?itemId=/content/journal/mgen/10.1099/mgen.0.000923&mimeType=html&fmt=ahah

References

  1. Sharma NC, Efstratiou A, Mokrousov I, Mutreja A, Das B et al. Diphtheria. Nat Rev Dis Primers 2019; 5:81 [View Article] [PubMed]
     [Google Scholar]
  2. Galazka A. The changing epidemiology of diphtheria in the vaccine era. J Infect Dis 2000; 181 Suppl 1:S2–9 [View Article]
     [Google Scholar]
  3. Vitek CR, Wharton M. Diphtheria in the former Soviet Union: reemergence of a pandemic disease. Emerg Infect Dis 1998; 4:539–550 [View Article] [PubMed]
     [Google Scholar]
  4. Matsuyama R, Akhmetzhanov AR, Endo A, Lee H, Yamaguchi T et al. Uncertainty and sensitivity analysis of the basic reproduction number of diphtheria: a case study of a Rohingya refugee camp in Bangladesh, November-December 2017. PeerJ 2018; 6:e4583 [View Article] [PubMed]
     [Google Scholar]
  5. Rahman MR, Islam K. Massive diphtheria outbreak among Rohingya refugees: lessons learnt. J Travel Med 2019; 26: [View Article] [PubMed]
     [Google Scholar]
  6. Badell E, Alharazi A, Criscuolo A, Almoayed KAA, Lefrancq N et al. Ongoing diphtheria outbreak in Yemen: a cross-sectional and genomic epidemiology study. Lancet Microbe 2021; 2:e386–e396 [View Article] [PubMed]
     [Google Scholar]
  7. Wagner KS, Stickings P, White JM, Neal S, Crowcroft NS et al. A review of the international issues surrounding the availability and demand for diphtheria antitoxin for therapeutic use. Vaccine 2009; 28:14–20 [View Article] [PubMed]
     [Google Scholar]
  8. Benamrouche N, Hasnaoui S, Badell E, Guettou B, Lazri M et al. Microbiological and molecular characterization of Corynebacterium diphtheriae isolated in Algeria between 1992 and 2015. Clin Microbiol Infect 2016; 22:1005 [View Article] [PubMed]
     [Google Scholar]
  9. Hennart M, Panunzi LG, Rodrigues C, Gaday Q, Baines SL et al. Population genomics and antimicrobial resistance in Corynebacterium diphtheriae. Genome Med 2020; 12:107 [View Article] [PubMed]
     [Google Scholar]
  10. Husada D, Soegianto SDP, Kurniawati IS, Hendrata AP, Irawan E et al. First-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae in Indonesia. BMC Infect Dis 2019; 19:1049 [View Article] [PubMed]
     [Google Scholar]
  11. Guglielmini J, Hennart M, Badell E, Toubiana J, Criscuolo A et al. Genomic epidemiology and strain taxonomy of Corynebacterium diphtheriae. J Clin Microbiol 2021; 59:e01581–21 [View Article]
     [Google Scholar]
  12. Will RC, Ramamurthy T, Sharma NC, Veeraraghavan B, Sangal L et al. Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae. Nat Commun 2021; 12:1500 [View Article] [PubMed]
     [Google Scholar]
  13. Barraud O, Badell E, Denis F, Guiso N, Ploy MC. Antimicrobial drug resistance in Corynebacterium diphtheriae mitis. Emerg Infect Dis 2011; 17:2078–2080 [View Article]
     [Google Scholar]
  14. Forde BM, Henderson A, Playford EG, Looke D, Henderson BC et al. Fatal respiratory diphtheria caused by ß-lactam–resistant Corynebacterium diphtheriae. Clin Infect Dis 2021; 73:e4531–e4538 [View Article]
     [Google Scholar]
  15. Tauch A, Kassing F, Kalinowski J, Pühler A. The Corynebacterium xerosis composite transposon Tn5432 consists of two identical insertion sequences, designated IS1249, flanking the erythromycin resistance gene ermCX. Plasmid 1995; 34:119–131 [View Article]
     [Google Scholar]
  16. Tauch A, Zheng Z, Pühler A, Kalinowski J. Corynebacterium striatum chloramphenicol resistance transposon Tn5564: genetic organization and transposition in Corynebacterium glutamicum. Plasmid 1998; 40:126–139 [View Article] [PubMed]
     [Google Scholar]
  17. Leyton B, Ramos JN, Baio PVP, Veras JFC, Souza C et al. Treat me well or will resist: uptake of mobile genetic elements determine the resistome of Corynebacterium striatum. Int J Mol Sci 2021; 22:7499 [View Article]
     [Google Scholar]
  18. Soriano F, Zapardiel J, Nieto E. Antimicrobial susceptibilities of Corynebacterium species and other non-spore-forming gram-positive bacilli to 18 antimicrobial agents. Antimicrob Agents Chemother 1995; 39:208–214 [View Article] [PubMed]
     [Google Scholar]
  19. Badell E, Guillot S, Tulliez M, Pascal M, Panunzi LG et al. Improved quadruplex real-time PCR assay for the diagnosis of diphtheria. J Med Microbiol 2019; 68:1455–1465 [View Article] [PubMed]
     [Google Scholar]
  20. Engler KH, Glushkevich T, Mazurova IK, George RC, Efstratiou A. A modified Elek test for detection of toxigenic corynebacteria in the diagnostic laboratory. J Clin Microbiol 1997; 35:495–498 [View Article] [PubMed]
     [Google Scholar]
  21. The European Committee onAntimicrobial Susceptibility Testing Breakpoint tables forinterpretation of MICs and zone diameters. Version 9.0; 2019 http://www.eucast.org
  22. https://www.sfm-microbiologie.org/wp-content/uploads/2020/07/CASFM_2013.pdf
  23. Criscuolo A, Brisse S. AlienTrimmer: a tool to quickly and accurately trim off multiple short contaminant sequences from high-throughput sequencing reads. Genomics 2013; 102:500–506 [View Article]
     [Google Scholar]
  24. Crusoe MR, Alameldin HF, Awad S, Boucher E, Caldwell A et al. The khmer software package: enabling efficient nucleotide sequence analysis. F1000Res 2015; 4:900 [View Article] [PubMed]
     [Google Scholar]
  25. Liu Y, Schröder J, Schmidt B. Musket: a multistage k-mer spectrum-based error corrector for Illumina sequence data. Bioinformatics 2013; 29:308–315 [View Article] [PubMed]
     [Google Scholar]
  26. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [View Article]
     [Google Scholar]
  27. Simão FA, Waterhouse RM, Ioannidis P, Kriventseva EV, Zdobnov EM. BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics 2015; 31:3210–3212 [View Article] [PubMed]
     [Google Scholar]
  28. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 2017; 13:e1005595 [View Article]
     [Google Scholar]
  29. Aziz RK, Bartels D, Best AA, DeJongh M, Disz T et al. The RAST Server: rapid annotations using subsystems technology. BMC Genomics 2008; 9:75 [View Article] [PubMed]
     [Google Scholar]
  30. Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 2020; 75:3491–3500 [View Article] [PubMed]
     [Google Scholar]
  31. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article] [PubMed]
     [Google Scholar]
  32. Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R et al. Circos: an information aesthetic for comparative genomics. Genome Res 2009; 19:1639–1645 [View Article] [PubMed]
     [Google Scholar]
  33. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res 2019; 47:W256–W259 [View Article] [PubMed]
     [Google Scholar]
  34. Santos AS, Ramos RT, Silva A, Hirata R Jr, Mattos-Guaraldi AL et al. Searching whole genome sequences for biochemical identification features of emerging and reemerging pathogenic Corynebacterium species. Funct Integr Genomics 2018; 18:593–610 [View Article] [PubMed]
     [Google Scholar]
  35. Nudel K, Zhao X, Basu S, Dong X, Hoffmann M et al. Genomics of Corynebacterium striatum, an emerging multidrug-resistant pathogen of immunocompromised patients. Clin Microbiol Infect 2018; 24:1016 [View Article]
     [Google Scholar]
  36. Grimont PAD, Grimont F, Efstratiou A, De Zoysa A, Mazurova I et al. International nomenclature for Corynebacterium diphtheriae ribotypes. Res Microbiol 2004; 155:162–166 [View Article] [PubMed]
     [Google Scholar]
  37. Paveenkittiporn W, Sripakdee S, Koobkratok O, Sangkitporn S, Kerdsin A. Molecular epidemiology and antimicrobial susceptibility of outbreak-associated Corynebacterium diphtheriae in Thailand, 2012. Infect Genet Evol 2019; 75:104007 [View Article] [PubMed]
     [Google Scholar]
  38. Chapartegui-González I, Fernández-Martínez M, Rodríguez-Fernández A, Rocha DJP, Aguiar E et al. Antimicrobial susceptibility and characterization of resistance mechanisms of Corynebacterium urealyticum clinical isolates. Antibiotics (Basel) 2020; 9:404 [View Article]
     [Google Scholar]
  39. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry 2014; 53:1565–1574 [View Article] [PubMed]
     [Google Scholar]
  40. Ahmad N, Hii SYF, Mohd Khalid MKN, Abd Wahab MA, Hashim R et al. First draft genome sequences of Malaysian clinical isolates of Corynebacterium diphtheriae. Genome Announc 2017; 5:e01670-16 [View Article]
     [Google Scholar]
  41. Dazas M, Badell E, Carmi-Leroy A, Criscuolo A, Brisse S. Taxonomic status of Corynebacterium diphtheriae biovar Belfanti and proposal of Corynebacterium belfantii sp. nov. Int J Syst Evol Microbiol 2018; 68:3826–3831 [View Article] [PubMed]
     [Google Scholar]
  42. Grosse-Kock S, Kolodkina V, Schwalbe EC, Blom J, Burkovski A et al. Genomic analysis of endemic clones of toxigenic and non-toxigenic Corynebacterium diphtheriae in Belarus during and after the major epidemic in 1990s. BMC Genomics 2017; 18:873 [View Article] [PubMed]
     [Google Scholar]
  43. Hoefer A, Pampaka D, Herrera-León S, Peiró S, Varona S et al. Molecular and epidemiological characterization of toxigenic and nontoxigenic Corynebacterium diphtheriae, Corynebacterium belfantii, Corynebacterium rouxii, and Corynebacterium ulcerans isolates identified in Spain from 2014 to 2019. J Clin Microbiol 2021; 59:e02410-20 [View Article]
     [Google Scholar]
  44. Mahomed S, Archary M, Mutevedzi P, Mahabeer Y, Govender P et al. An isolated outbreak of diphtheria in South Africa, 2015. Epidemiol Infect 2017; 145:2100–2108 [View Article] [PubMed]
     [Google Scholar]
  45. Lodeiro-Colatosti A, Reischl U, Holzmann T, Hernández-Pereira CE, Rísquez A et al. Diphtheria outbreak in Amerindian Communities, Wonken, Venezuela, 2016-2017. Emerg Infect Dis 2018; 24:1340–1344 [View Article]
     [Google Scholar]
  46. Strauss RA, Herrera-Leon L, Guillén AC, Castro JS, Lorenz E et al. Molecular and epidemiologic characterization of the diphtheria outbreak in Venezuela. Sci Rep 2021; 11:6378 [View Article] [PubMed]
     [Google Scholar]
  47. Tedijanto C, Olesen SW, Grad YH, Lipsitch M. Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora. Proc Natl Acad Sci U S A 2018; 115:E11988–E11995 [View Article] [PubMed]
     [Google Scholar]
  48. Mina NV, Burdz T, Wiebe D, Rai JS, Rahim T et al. Canada’s first case of a multidrug-resistant Corynebacterium diphtheriae strain, isolated from a skin abscess. J Clin Microbiol 2011; 49:4003–4005 [View Article] [PubMed]
     [Google Scholar]
  49. Lundborg CS, Tamhankar AJ. Antibiotic residues in the environment of South East Asia. BMJ 2017; 358:j2440 [View Article] [PubMed]
     [Google Scholar]
  50. Sierra JM, Martinez-Martinez L, Vázquez F, Giralt E, Vila J. Relationship between mutations in the gyrA gene and quinolone resistance in clinical isolates of Corynebacterium striatum and Corynebacterium amycolatum. Antimicrob Agents Chemother 2005; 49:1714–1719 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000923
Loading
Multidrug-resistant toxigenic Corynebacterium diphtheriae sublineage 453 with two novel resistance genomic islands
M Gen 9, 000923 (2023); https://doi.org/10.1099/mgen.0.000923
/content/journal/mgen/10.1099/mgen.0.000923
/content/journal/mgen/10.1099/mgen.0.000923
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error