1887

Abstract

The emerging strain BI/NAP1/027 has been reported to be associated with more severe clinical symptoms and higher mortality rates, thought in part due to production of a novel binary toxin alongside conventional A and B toxins. However, recent studies suggest that this may not always be the case. Therefore, the purpose of this report was to investigate the correlation between clinical severity and microbiological characteristics of CDT-producing isolates in Japan. Eight Japanese isolates of CDT producing were investigated using genotyping, cytotoxic activity assays and toxin gene expression. Correlation with clinical severity was performed retrospectively using the patient record. Three of eight patients were assessed as having severe infection (CDI). PCR ribotyping resolved six ribotypes including ribotype 027. No specific genes were identified determining severe compared with non-severe cases. Positive correlation of expression levels of , and were observed although these expression levels were not correlated with cytotoxicity. CDI severity index neither correlated with toxin gene expression level nor cytotoxicity. These data indicate that the possession of the CDT gene and toxin gene expression levels may not relate to cytotoxicity or clinical severity.

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2022-10-20
2024-07-25
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References

  1. Kelly CP, LaMont JT. Clostridium difficile infection. Annu Rev Med 1998; 49:375–390 [View Article] [PubMed]
    [Google Scholar]
  2. Lyerly DM, Krivan HC, Wilkins TD. Clostridium difficile: its disease and toxins. Clin Microbiol Rev 1988; 1:1–18 [View Article] [PubMed]
    [Google Scholar]
  3. Schirmer J, Aktories K. Large clostridial cytotoxins: cellular biology of Rho/Ras-glucosylating toxins. Biochim Biophys Acta 2004; 1673:66–74 [View Article] [PubMed]
    [Google Scholar]
  4. Loo VG, Poirier L, Miller MA, Oughton M, Libman MD et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353:2442–2449 [View Article] [PubMed]
    [Google Scholar]
  5. Warny M, Pepin J, Fang A, Killgore G, Thompson A et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005; 366:1079–1084 [View Article] [PubMed]
    [Google Scholar]
  6. Geric B, Rupnik M, Gerding DN, Grabnar M, Johnson S. Distribution of Clostridium difficile variant toxinotypes and strains with binary toxin genes among clinical isolates in an American hospital. J Med Microbiol 2004; 53:887–894 [View Article]
    [Google Scholar]
  7. Pépin J, Valiquette L, Alary M-E, Villemure P, Pelletier A et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 2004; 171:466–472 [View Article]
    [Google Scholar]
  8. Eggertson L. Quebec strain of C. difficile in 7 provinces. CMAJ 2006; 174:607–608 [View Article]
    [Google Scholar]
  9. Redelings MD, Sorvillo F, Mascola L. Increase in Clostridium difficile-related mortality rates, United States, 1999-2004. Emerg Infect Dis 2007; 13:1417–1419 [View Article]
    [Google Scholar]
  10. McDonald LC, Killgore GE, Thompson A, Owens RC, Kazakova SV et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353:2433–2441 [View Article]
    [Google Scholar]
  11. Bauer MP, Notermans DW, van Benthem BHB, Brazier JS, Wilcox MH et al. Clostridium difficile infection in Europe: a hospital-based survey. Lancet 2011; 377:63–73 [View Article] [PubMed]
    [Google Scholar]
  12. Usui M, Nanbu Y, Oka K, Takahashi M, Tamura Y et al. Genetic relatedness between Japanese and European isolates of Clostridium difficile originating from piglets and their risk associated with human health. Front Microbiol 2014; 5:513 [View Article] [PubMed]
    [Google Scholar]
  13. Collins DA, Hawkey PM, Riley TV. Epidemiology of Clostridium difficile infection in Asia. Antimicrob Resist Infect Control 2013; 2:21 [View Article] [PubMed]
    [Google Scholar]
  14. Miller M, Gravel D, Mulvey M, Taylor G, Boyd D et al. Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis 2010; 50:194–201 [View Article] [PubMed]
    [Google Scholar]
  15. Walk ST, Micic D, Jain R, Lo ES, Trivedi I et al. Clostridium difficile ribotype does not predict severe infection. Clin Infect Dis 2012; 55:1661–1668 [View Article] [PubMed]
    [Google Scholar]
  16. Zar FA, Bakkanagari SR, Moorthi KMLST, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007; 45:302–307 [View Article] [PubMed]
    [Google Scholar]
  17. Kajitani R, Toshimoto K, Noguchi H, Toyoda A, Ogura Y et al. Efficient de novo assembly of highly heterozygous genomes from whole-genome shotgun short reads. Genome Res 2014; 24:1384–1395 [View Article] [PubMed]
    [Google Scholar]
  18. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  19. Griffiths D, Fawley W, Kachrimanidou M, Bowden R, Crook DW et al. Multilocus sequence typing of Clostridium difficile. J Clin Microbiol 2010; 48:770–778 [View Article] [PubMed]
    [Google Scholar]
  20. Darling ACE, Mau B, Blattner FR, Perna NT. Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res 2004; 14:1394–1403 [View Article] [PubMed]
    [Google Scholar]
  21. Li W, Godzik A. Cd-hit: A fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22:1658–1659 [View Article]
    [Google Scholar]
  22. Chen L, Yang J, Yu J, Yao Z, Sun L et al. VFDB: a reference database for bacterial virulence factors. Nucleic Acids Res 2005; 33:D325–8 [View Article]
    [Google Scholar]
  23. McArthur AG, Waglechner N, Nizam F, Yan A, Azad MA et al. The comprehensive antibiotic resistance database. Antimicrob Agents Chemother 2013; 57:3348–3357 [View Article]
    [Google Scholar]
  24. Oka K, Osaki T, Hanawa T, Kurata S, Kamiya S et al. Molecular and microbiological characterization of clostridium difficile isolates from single, relapse, and reinfection cases. J Clin Microbiol 2012; 50:915–921 [View Article]
    [Google Scholar]
  25. Persson S, Torpdahl M, Olsen KEP. New multiplex PCR method for the detection of Clostridium difficile toxin A (tcdA) and toxin B (tcdB) and the binary toxin (cdtA/cdtB) genes applied to A Danish strain collection. Clin Microbiol Infect 2008; 14:1057–1064 [View Article]
    [Google Scholar]
  26. Persson S, Jensen JN, Olsen KEP. Multiplex PCR method for detection of Clostridium difficile tcdA, tcdB, cdtA, and cdtB and internal in-frame deletion of tcdC. J Clin Microbiol 2011; 49:4299–4300 [View Article] [PubMed]
    [Google Scholar]
  27. Wroblewski D, Hannett GE, Bopp DJ, Dumyati GK, Halse TA et al. Rapid molecular characterization of Clostridium difficile and assessment of populations of C. difficile in stool specimens. J Clin Microbiol 2009; 47:2142–2148 [View Article] [PubMed]
    [Google Scholar]
  28. Woo TDH, Oka K, Takahashi M, Hojo F, Kamiya S et al. Inhibition of the cytotoxic effect of Clostridium difficile in vitro by Clostridium butyricum MIYAIRI 588 strain. J Med Microbiol 2011; 60:1617–1625 [View Article] [PubMed]
    [Google Scholar]
  29. Merrigan M, Venugopal A, Mallozzi M, Roxas B, Viswanathan VK et al. Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production. J Bacteriol 2010; 192:4904–4911 [View Article] [PubMed]
    [Google Scholar]
  30. Kato H, Senoh M, Honda H, Fukuda T, Tagashira Y et al. Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study. Anaerobe 2019; 60:102011 [View Article] [PubMed]
    [Google Scholar]
  31. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108:478–498 [View Article] [PubMed]
    [Google Scholar]
  32. Pépin J, Routhier S, Gagnon S, Brazeau I. Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis 2006; 42:758–764 [View Article] [PubMed]
    [Google Scholar]
  33. Keddis MT, Khanna S, Noheria A, Baddour LM, Pardi DS et al. Clostridium difficile infection in patients with chronic kidney disease. Mayo Clin Proc 2012; 87:1046–1053 [View Article] [PubMed]
    [Google Scholar]
  34. Eddi R, Malik MN, Shakov R, Baddoura WJ, Chandran C et al. Chronic kidney disease as a risk factor for Clostridium difficile infection. Nephrology (Carlton) 2010; 15:471–475 [View Article] [PubMed]
    [Google Scholar]
  35. Jacob SS, Sebastian JC, Hiorns D, Jacob S, Mukerjee PK. Clostridium difficile and acute respiratory distress syndrome. Heart Lung 2004; 33:265–268 [View Article] [PubMed]
    [Google Scholar]
  36. Tamma PD, Sandora TJ. Clostridium difficile infection in children: current state and unanswered questions. J Pediatric Infect Dis Soc 2012; 1:230–243 [View Article] [PubMed]
    [Google Scholar]
  37. Mardaneh J, Mohammadzadeh A, Bagheri S, Baniasadi M, Anvarinejad M et al. Toxigenic Clostridium difficile infection in children: performance of toxin A/B immunoassay. Crescent J Med Biol Sci 2021122–126
    [Google Scholar]
  38. Bolton RP, Tait SK, Dear PR, Losowsky MS. Asymptomatic neonatal colonisation by Clostridium difficile. Arch Dis Child 1984; 59:466–472 [View Article] [PubMed]
    [Google Scholar]
  39. Iwashima Y, Nakamura A, Kato H, Kato H, Wakimoto Y et al. A retrospective study of the epidemiology of Clostridium difficile infection at A University Hospital in Japan: genotypic features of the isolates and clinical characteristics of the patients. J Infect Chemother 2010; 16:329–333 [View Article] [PubMed]
    [Google Scholar]
  40. Goorhuis A, Bakker D, Corver J, Debast SB, Harmanus C et al. Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis 2008; 47:1162–1170 [View Article] [PubMed]
    [Google Scholar]
  41. Curry SR, Marsh JW, Muto CA, O’Leary MM, Pasculle AW et al. tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile. J Clin Microbiol 2007; 45:215–221 [View Article] [PubMed]
    [Google Scholar]
  42. Murray R, Boyd D, Levett PN, Mulvey MR, Alfa MJ. Truncation in the tcdC region of the Clostridium difficile PathLoc of clinical isolates does not predict increased biological activity of Toxin B or Toxin A. BMC Infect Dis 2009; 9:103 [View Article] [PubMed]
    [Google Scholar]
  43. Verdoorn BP, Orenstein R, Rosenblatt JE, Sloan LM, Schleck CD et al. High prevalence of tcdC deletion-carrying Clostridium difficile and lack of association with disease severity. Diagn Microbiol Infect Dis 2010; 66:24–28 [View Article] [PubMed]
    [Google Scholar]
  44. Goldenberg SD, French GL. Lack of association of tcdC type and binary toxin status with disease severity and outcome in toxigenic Clostridium difficile. J Infect 2011; 62:355–362 [View Article] [PubMed]
    [Google Scholar]
  45. Valiente E, Dawson LF, Cairns MD, Stabler RA, Wren BW. Emergence of new PCR ribotypes from the hypervirulent Clostridium difficile 027 lineage. J Med Microbiol 2012; 61:49–56 [View Article] [PubMed]
    [Google Scholar]
  46. Knetsch CW, Hensgens MPM, Harmanus C, van der Bijl MW, Savelkoul PHM et al. Genetic markers for Clostridium difficile lineages linked to hypervirulence. Microbiology (Reading) 2011; 157:3113–3123 [View Article] [PubMed]
    [Google Scholar]
  47. Usui Y, Nukui Y, Koike R, Tohda S, Saito R. Draft genome sequence of a Clostridioides difficile sequence type 97 strain belonging to hypervirulent clade 2. Microbiol Resour Announc 2020; 9:e00245-20 [View Article] [PubMed]
    [Google Scholar]
  48. Sawabe E, Kato H, Osawa K, Chida T, Tojo N et al. Molecular analysis of Clostridium difficile at a university teaching hospital in Japan: a shift in the predominant type over a five-year period. Eur J Clin Microbiol Infect Dis 2007; 26:695–703 [View Article] [PubMed]
    [Google Scholar]
  49. Krutova M, Nyc O, Matejkova J, Kuijper EJ, Jalava J et al. The recognition and characterisation of Finnish Clostridium difficile isolates resembling PCR-ribotype 027. J Microbiol Immunol Infect 2018; 51:344–351 [View Article] [PubMed]
    [Google Scholar]
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