Penicillin Binding Protein Substitutions Cooccur with Fluoroquinolone Resistance in Epidemic Lineages of Multidrug-Resistant Clostridioides difficile

Author:

Dingle Kate E.12ORCID,Freeman Jane34,Didelot Xavier5ORCID,Quan T. Phuong12ORCID,Eyre David W.26,Swann Jeremy12,Spittal William D.34,Clark Emma V.34,Jolley Keith A.7,Walker A. Sarah12,Wilcox Mark H.34,Crook Derrick W.12

Affiliation:

1. Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford University, Oxford, United Kingdom

2. National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom

3. Department of Microbiology, Leeds Teaching Hospitals Trust, Leeds, United Kingdom

4. Healthcare Associated Infections Research Group, The Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom

5. School of Life Sciences and Department of Statistics, University of Warwick, Coventry, United Kingdom

6. Big Data Institute, Nuffield Department of Population Health, Oxford University of Oxford, Oxford, United Kingdom

7. Department of Biology, University of Oxford, Oxford, United Kingdom

Abstract

Fluoroquinolone and cephalosporin use in healthcare settings has triggered outbreaks of high-mortality, multidrug-resistant C. difficile infection. Here, we identify a mechanism associated with raised cephalosporin MICs in C. difficile comprising amino acid substitutions in two cell wall transpeptidase enzymes (penicillin binding proteins).

Funder

National Institute for Health Research (NIHR) Oxford, UK

National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance

NIHR Health Protection Research Unit in Genomics and Enabling Data

National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections

National Institute for Health Research Leeds in Vitro Diagnostics Co-operative

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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