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Front. Public Health | doi: 10.3389/fpubh.2019.00309

Development and implementation of whole genome sequencing-based typing schemes for Clostridioides difficile

  • 1National Laboratory of Health, Environment and Food, Slovenia
  • 2Faculty of Medicine, University of Maribor, Slovenia

Clostridioides difficile is an important nosocomial pathogen increasingly observed in the community and in different non-human reservoirs. The epidemiology and transmissibility of C. difficile has been studied using a variety of typing methods, including more recently developed whole-genome sequence (WGS) analysis that is becoming used routinely for bacterial typing worldwide. Here we review the schemes for WGS-based typing methods available for C. difficile and their applications in the field of human C. difficile infection (CDI).
The two main approaches to discover genomic variations are single nucleotide variant (SNV) analysis and methods based on gene-by-gene comparisons (frequently called core genome or whole genome MLST, cgMLST or wgMLST). SNV analysis currently provides the ultimate resolution, however, typing nomenclature and standardized methodology are missing. On the other hand, gene-by-gene approaches allow portability and standardized nomenclature, and are therefore becoming increasingly popular in bacterial epidemiology and outbreak investigation. Two commercial software packages (BioNumerics and Ridom SeqSphere+) and an open source database (EnteroBase) for allele and sequence type determination for C. difficile are currently available.
Proof-of-concept WGS studies have already enabled advances in the investigation of the population structure of C. difficile species, microevolution within the epidemic strains, intercontinental transmission over time and in tracking of transmission events. WGS of clinical C. difficile isolates demonstrated a considerable genetic diversity suggesting diverse reservoirs for CDI. WGS was also shown to aid in resolving relapses and reinfections in recurrent CDI and has potential for use as a tool for assessing hospital infection prevention and control performance.

The proof-of-concept WGS studies have already enabled advances in the investigation of the population structure of C. difficile species, microevolution within the epidemic strains, intercontinental transmission over time and in tracking of transmission events. Whole-genome sequencing of clinical C. difficile isolates demonstrated a considerable genetic diversity suggesting diverse reservoirs for CDI. WGS was also shown to aid in resolving relapses and reinfections in recurrent CDI and a potential to be used as a tool for assessing hospital infection control performance.

Keywords: Clostridioides (Clostridium) difficile, wgMLST, cgMLST, typing, CDI, SNV

Received: 31 May 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Janezic and Rupnik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sandra Janezic, National Laboratory of Health, Environment and Food, Maribor, Slovenia, sandra.janezic@nlzoh.si