Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.

Corynebacterium diphtheriae is the etiological agent of diphtheria, a disease caused by the presence of the diphtheria toxin. However, an increasing number of records report non-toxigenic C. diphtheriae infections. Here, a C. diphtheriae strain was recovered from a patient with a past history of bro...

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Main Authors: Florian Tagini, Trestan Pillonel, Antony Croxatto, Claire Bertelli, Angela Koutsokera, Alban Lovis, Gilbert Greub
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-08-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2018.01743/full
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author Florian Tagini
Trestan Pillonel
Antony Croxatto
Claire Bertelli
Angela Koutsokera
Alban Lovis
Gilbert Greub
Gilbert Greub
author_facet Florian Tagini
Trestan Pillonel
Antony Croxatto
Claire Bertelli
Angela Koutsokera
Alban Lovis
Gilbert Greub
Gilbert Greub
author_sort Florian Tagini
collection DOAJ
description Corynebacterium diphtheriae is the etiological agent of diphtheria, a disease caused by the presence of the diphtheria toxin. However, an increasing number of records report non-toxigenic C. diphtheriae infections. Here, a C. diphtheriae strain was recovered from a patient with a past history of bronchiectasis who developed a severe tracheo-bronchitis with multiple whitish lesions of the distal trachea and the mainstem bronchi. Whole-genome sequencing (WGS), performed in parallel with PCR targeting the toxin gene and the Elek test, provided clinically relevant results in a short turnaround time, showing that the isolate was non-toxigenic. A comparative genomic analysis of the new strain (CHUV2995) with 56 other publicly available genomes of C. diphtheriae revealed that the strains CHUV2995, CCUG 5865 and CMCNS703 share a lower average nucleotide identity (ANI) (95.24 to 95.39%) with the C. diphtheriae NCTC 11397T reference genome than all other C. diphtheriae genomes (>98.15%). Core genome phylogeny confirmed the presence of two monophyletic clades. Based on these findings, we propose here two new C. diphtheriae subspecies to replace the lineage denomination used in previous multilocus sequence typing studies: C. diphtheriae subsp. lausannense subsp. nov. (instead of lineage-2), regrouping strains CHUV2995, CCUG 5865, and CMCNS703, and C. diphtheriae subsp. diphtheriae subsp. nov, regrouping all other C. diphtheriae in the dataset (instead of lineage-1). Interestingly, members of subspecies lausannense displayed a larger genome size than subspecies diphtheriae and were enriched in COG categories related to transport and metabolism of lipids (I) and inorganic ion (P). Conversely, they lacked all genes involved in the synthesis of pili (SpaA-type, SpaD-type and SpaH-type), molybdenum cofactor and of the nitrate reductase. Finally, the CHUV2995 genome is particularly enriched in mobility genes and harbors several prophages. The genome encodes a type II-C CRISPR-Cas locus with 2 spacers that lacks csn2 or cas4, which could hamper the acquisition of new spacers and render strain CHUV2995 more susceptible to bacteriophage infections and gene acquisition through various mechanisms of horizontal gene transfer.
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spelling doaj.art-83728d058a8d4a3191d5321a00c922262022-12-22T02:04:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-08-01910.3389/fmicb.2018.01743385169Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.Florian Tagini0Trestan Pillonel1Antony Croxatto2Claire Bertelli3Angela Koutsokera4Alban Lovis5Gilbert Greub6Gilbert Greub7Institute of Microbiology, Department of Laboratory Medicine, Lausanne University Hospital, Lausanne University, Lausanne, SwitzerlandInstitute of Microbiology, Department of Laboratory Medicine, Lausanne University Hospital, Lausanne University, Lausanne, SwitzerlandInstitute of Microbiology, Department of Laboratory Medicine, Lausanne University Hospital, Lausanne University, Lausanne, SwitzerlandInstitute of Microbiology, Department of Laboratory Medicine, Lausanne University Hospital, Lausanne University, Lausanne, SwitzerlandDivision of Pulmonology, Department of Medicine, Lausanne University Hospital, Lausanne, SwitzerlandDivision of Pulmonology, Department of Medicine, Lausanne University Hospital, Lausanne, SwitzerlandInstitute of Microbiology, Department of Laboratory Medicine, Lausanne University Hospital, Lausanne University, Lausanne, SwitzerlandDivision of Infectious Diseases, Department of Medicine, Lausanne University Hospital, Lausanne, SwitzerlandCorynebacterium diphtheriae is the etiological agent of diphtheria, a disease caused by the presence of the diphtheria toxin. However, an increasing number of records report non-toxigenic C. diphtheriae infections. Here, a C. diphtheriae strain was recovered from a patient with a past history of bronchiectasis who developed a severe tracheo-bronchitis with multiple whitish lesions of the distal trachea and the mainstem bronchi. Whole-genome sequencing (WGS), performed in parallel with PCR targeting the toxin gene and the Elek test, provided clinically relevant results in a short turnaround time, showing that the isolate was non-toxigenic. A comparative genomic analysis of the new strain (CHUV2995) with 56 other publicly available genomes of C. diphtheriae revealed that the strains CHUV2995, CCUG 5865 and CMCNS703 share a lower average nucleotide identity (ANI) (95.24 to 95.39%) with the C. diphtheriae NCTC 11397T reference genome than all other C. diphtheriae genomes (>98.15%). Core genome phylogeny confirmed the presence of two monophyletic clades. Based on these findings, we propose here two new C. diphtheriae subspecies to replace the lineage denomination used in previous multilocus sequence typing studies: C. diphtheriae subsp. lausannense subsp. nov. (instead of lineage-2), regrouping strains CHUV2995, CCUG 5865, and CMCNS703, and C. diphtheriae subsp. diphtheriae subsp. nov, regrouping all other C. diphtheriae in the dataset (instead of lineage-1). Interestingly, members of subspecies lausannense displayed a larger genome size than subspecies diphtheriae and were enriched in COG categories related to transport and metabolism of lipids (I) and inorganic ion (P). Conversely, they lacked all genes involved in the synthesis of pili (SpaA-type, SpaD-type and SpaH-type), molybdenum cofactor and of the nitrate reductase. Finally, the CHUV2995 genome is particularly enriched in mobility genes and harbors several prophages. The genome encodes a type II-C CRISPR-Cas locus with 2 spacers that lacks csn2 or cas4, which could hamper the acquisition of new spacers and render strain CHUV2995 more susceptible to bacteriophage infections and gene acquisition through various mechanisms of horizontal gene transfer.https://www.frontiersin.org/article/10.3389/fmicb.2018.01743/fullnon-toxigenic diphtheriacomparative genomicsvirulencemobile genetic elementsCRISPRpili
spellingShingle Florian Tagini
Trestan Pillonel
Antony Croxatto
Claire Bertelli
Angela Koutsokera
Alban Lovis
Gilbert Greub
Gilbert Greub
Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.
Frontiers in Microbiology
non-toxigenic diphtheria
comparative genomics
virulence
mobile genetic elements
CRISPR
pili
title Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.
title_full Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.
title_fullStr Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.
title_full_unstemmed Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.
title_short Distinct Genomic Features Characterize Two Clades of Corynebacterium diphtheriae: Proposal of Corynebacterium diphtheriae Subsp. diphtheriae Subsp. nov. and Corynebacterium diphtheriae Subsp. lausannense Subsp. nov.
title_sort distinct genomic features characterize two clades of corynebacterium diphtheriae proposal of corynebacterium diphtheriae subsp diphtheriae subsp nov and corynebacterium diphtheriae subsp lausannense subsp nov
topic non-toxigenic diphtheria
comparative genomics
virulence
mobile genetic elements
CRISPR
pili
url https://www.frontiersin.org/article/10.3389/fmicb.2018.01743/full
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