Clostridioides difficile PCR ribotype 151 is polyphyletic and includes pathogenic isolates from cryptic clade C-II with mono-toxin pathogenicity loci that can escape routine diagnostics
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
ABSTRACT We report a patient case with pseudomembranous colitis associated with a mono-toxin producing Clostridioides difficile belonging to the very rarely diagnosed PCR ribotype (RT) 151. The infection was difficult to diagnose, since the isolate and the feces sample tested negative for toxin-encoding genes using a routine commercial test. This prompted us to sequence n = 11 RT151s from various geographical regions to study their genomic characteristics and relatedness. By including whole genome sequence data from other sources, we could further place these isolates into the phylogenetic tree of C. difficile and assign them to their respective clades. These analyses revealed that 1) RT151s are polyphyletic with isolates falling into clades 1, and cryptic clades C-I and C-II 2) RT151 contains both non-toxigenic and toxigenic isolates and 3) RT151 C-II isolates contained mono-toxin pathogenicity loci (PaLoc). Additional analysis with PacBio circular consensus sequencing revealed that the isolate from our patient case report contains a novel PaLoc insertion site, lacked tcdA and a had significantly divergent tcdB sequence that might explain the failure of the diagnostic test. The study is noteworthy as 1) RT151 encompasses both typical and cryptic clades and 2) conclusive evidence for CDI due to clade C-II isolates was hitherto lacking.
Authors 10
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Quinten R. Ducarmon Aachen Center for Microbiome Analyses and Therapeutics Department of Medical Microbiology Center for Microiome Analyses and Therapeutics Deprtment of Medicl Microbiology
Leiden University · Leiden University Medical Center
Affiliation as printed
Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Center for Microiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands
Department of Medial Mirobiology, University Medial Centre Utreht, Utreht, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands
Department of Haematology, University Meical Centre Utrecht, Utrecht, The Netherlans
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands
Department of Medial Mirobiology, University Medial Centre Utreht, Utreht, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Leiden Genome Technology Center, Leiden University Medical Center, Leiden, The Netherlands
Lidn Gnom Tchnology Cntr, Lidn Univrsity Mdical Cntr, Lidn, Th Nthrlands
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Leiden University Medical Center
Affiliation as printed
Leiden Genome Technology Center, Leiden University Medical Center, Leiden, The Netherlands
Lidn Gnom Tchnology Cntr, Lidn Univrsity Mdical Cntr, Lidn, Th Nthrlands
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Ed J. Kuijper Aachen Center for Microbiome Analyses and Therapeutics Department of Medical Microbiology Center for Microiome Analyses and Therapeutics Deprtment of Medicl Microbiology
Leiden University · Leiden University Medical Center · National Institute for Public Health and the Environment
Affiliation as printed
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Center for Microiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Center or Inectious Disease Control, National Institute or Public Health and the Environment, Bilthoven, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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Wiep Klaas Smits corresponding Aachen Center for Microbiome Analyses and Therapeutics Department of Medical Microbiology Center for Microiome Analyses and Therapeutics Deprtment of Medicl Microbiology
Leiden University · Leiden University Medical Center
Affiliation as printed
Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Centre for Microbial Cell Biology, Leiden, The Netherlands
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Center for Microiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Centre for Microbial Cell Bioloy, Leiden, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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