Tracing the Spread of Clostridium difficile Ribotype 027 in Germany Based on Bacterial Genome Sequences

Matthias Steglich; Andreas Nitsche; Lutz von Müller; Mathias Herrmann; Thomas A Kohl; Stefan Niemann; Ulrich Nübel

doi:10.1371/journal.pone.0139811

Tracing the Spread of Clostridium difficile Ribotype 027 in Germany Based on Bacterial Genome Sequences

PLoS One. 2015 Oct 7;10(10):e0139811. doi: 10.1371/journal.pone.0139811. eCollection 2015.

Authors

Matthias Steglich¹, Andreas Nitsche², Lutz von Müller³, Mathias Herrmann³, Thomas A Kohl⁴, Stefan Niemann⁵, Ulrich Nübel⁶

Affiliations

¹ Robert Koch Institute, Department of Infectious Diseases, Division of Nosocomial Pathogens and Antibiotic Resistances, Wernigerode, Germany.
² Robert Koch Institute, Centre for Biological Threats and Special Pathogens, ZBS 1 Highly Pathogenic Viruses, Berlin, Germany.
³ University of Saarland Medical Centre, Institute of Medical Microbiology and Hygiene, National Consultant Laboratory for Clostridium difficile, Homburg, Germany.
⁴ Research Center Borstel, Molecular Mycobacteriology, Borstel, Germany.
⁵ Research Center Borstel, Molecular Mycobacteriology, Borstel, Germany; German Center for Infection Research (DZIF), Partner Site Borstel, Borstel, Germany.
⁶ Leibniz Institute DSMZ, Department of Microbial Genome Research, Braunschweig, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany.

Abstract

We applied whole-genome sequencing to reconstruct the spatial and temporal dynamics underpinning the expansion of Clostridium difficile ribotype 027 in Germany. Based on re-sequencing of genomes from 57 clinical C. difficile isolates, which had been collected from hospitalized patients at 36 locations throughout Germany between 1990 and 2012, we demonstrate that C. difficile genomes have accumulated sequence variation sufficiently fast to document the pathogen's spread at a regional scale. We detected both previously described lineages of fluoroquinolone-resistant C. difficile ribotype 027, FQR1 and FQR2. Using Bayesian phylogeographic analyses, we show that fluoroquinolone-resistant C. difficile 027 was imported into Germany at least four times, that it had been widely disseminated across multiple federal states even before the first outbreak was noted in 2007, and that it has continued to spread since.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / therapeutic use
Bacterial Proteins / genetics
Bayes Theorem
Clostridioides difficile / drug effects
Clostridioides difficile / genetics*
Clostridioides difficile / isolation & purification*
Enterocolitis, Pseudomembranous / drug therapy
Enterocolitis, Pseudomembranous / microbiology
Fluoroquinolones / therapeutic use
Genetic Variation / genetics
Genome, Bacterial / genetics*
Germany
Hospitalization
Humans
Microbial Sensitivity Tests / methods
Phylogeography / methods
Ribotyping / methods

Substances

Anti-Bacterial Agents
Bacterial Proteins
Fluoroquinolones

Grants and funding

The National Consultant Laboratory for Clostridium difficile at the University of Saarland Medical Centre in Homburg was partially funded by a grant from the Robert Koch Institute (to MH). The work of MS was funded through a PhD stipend from the Robert Koch Institute (to UN). This work was partially funded by the European Union, project PathNgenTrace (FP7-278864-2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.