The recent emergence of a highly related virulent Clostridium difficile clade with unique characteristics

Shaw, H.A.; Preston, M.D.; Vendrik, K.E.W.; Cairns, M.D.; Browne, H.P.; Stabler, R.A.; ... ; Wren, B.W. (2020)

Article / Letter to editor

Objectives: Clostridium difficile is a major global human pathogen divided into five clades, of which Glade 3 is the least characterized and consists predominantly of PCR ribotype (RT) 023 strains. Our aim was to analyse and characterize this Glade.Methods: In this cohort study the clinical presentation of C. difficile RT023 infections was analysed in comparison with known 'hypervirulent' and non-hypervirulent strains, using data from the Netherlands national C. difficile surveillance programme. European RT023 strains of diverse origin were collected and whole-genome sequenced to determine the genetic similarity between isolates. Distinctive features were investigated and characterized.Results: Clinical presentation of C. difficile RT023 infections show severe infections akin to those seen with 'hypervirulent' strains from clades 2 (RT027) and 5 (RT078) (35%, 29% and 27% severe CDI, respectively), particularly with significantly more bloody diarrhoea than RT078 and non-hypervirulent strains (RT023 8%, other RTs 4%, p 0.036). The full genome sequence of strain CD305 is presented as a robust reference. Phylogenetic comparison of CD305 and a further 79 previously uncharacterized European RT023 strains of diverse origin revealed minor genetic divergence with >99.8% pairwise identity between strains. Analyses revealed distinctive features among Glade 3 strains, including conserved pathogenicity locus, binary toxin and phage insertion toxin genotypes, glycosylation of S-layer proteins, presence of the RT078 four-gene trehalose cluster and an esculinase-negative genotype.Conclusions: Given their recent emergence, virulence and genomic characteristics, the surveillance of Glade 3 strains should be more highly prioritized. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

• Clostridium difficile
• Clostridium difficile infection
• Next-generation sequencing
• RT023
• Trehalose
• S-layer
• Clade 3

• All authors: Shaw, H.A.; Preston, M.D.; Vendrik, K.E.W.; Cairns, M.D.; Browne, H.P.; Stabler, R.A.; Crobach, M.J.T.; Corver, J.; Pituch, H.; Ingebretsen, A.; Pirmohamed, M.; Faulds-Pain, A.; Valiente, E.; Lawley, T.D.; Fairweather, N.F.; Kuijper, E.J.; Wren, B.W.
• Date: 2020-04-01
• Journal: Clinical Microbiology and Infection
• Volume: 26
• Issue: 4
• Pages: 492 - 498
• DOI: doi:10.1016/j.cmi.2019.09.004
• Link: https://www.sciencedirect.com/science/article/pii/S1198743X19304896?via%...